CN114748498A - Application of shRNA aiming at CBFbeta in preparation of colorectal cancer treatment drug - Google Patents
Application of shRNA aiming at CBFbeta in preparation of colorectal cancer treatment drug Download PDFInfo
- Publication number
- CN114748498A CN114748498A CN202210516955.7A CN202210516955A CN114748498A CN 114748498 A CN114748498 A CN 114748498A CN 202210516955 A CN202210516955 A CN 202210516955A CN 114748498 A CN114748498 A CN 114748498A
- Authority
- CN
- China
- Prior art keywords
- colorectal cancer
- cbf
- cbfbeta
- beta
- expression
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 37
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims abstract description 36
- 239000004055 small Interfering RNA Substances 0.000 title claims abstract description 10
- 108091027967 Small hairpin RNA Proteins 0.000 title claims abstract description 9
- 239000003814 drug Substances 0.000 title claims abstract description 8
- 229940079593 drug Drugs 0.000 title description 2
- QHRCVGXBBIRPTE-UHFFFAOYSA-N 5-ethyl-4-(4-methoxyphenyl)-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC(OC)=CC=2)=C1CC QHRCVGXBBIRPTE-UHFFFAOYSA-N 0.000 abstract description 42
- 230000014509 gene expression Effects 0.000 abstract description 12
- 206010028980 Neoplasm Diseases 0.000 abstract description 11
- 108090000623 proteins and genes Proteins 0.000 abstract description 10
- 102000015775 Core Binding Factor Alpha 1 Subunit Human genes 0.000 abstract description 9
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 abstract description 9
- 230000012010 growth Effects 0.000 abstract description 9
- 230000035897 transcription Effects 0.000 abstract description 8
- 238000013518 transcription Methods 0.000 abstract description 8
- 238000011161 development Methods 0.000 abstract description 5
- 230000035755 proliferation Effects 0.000 abstract description 5
- 101000613820 Homo sapiens Osteopontin Proteins 0.000 abstract description 4
- 101000979460 Homo sapiens Protein Niban 1 Proteins 0.000 abstract description 4
- 101000644174 Homo sapiens Uridine phosphorylase 1 Proteins 0.000 abstract description 4
- 206010027476 Metastases Diseases 0.000 abstract description 4
- 102100040557 Osteopontin Human genes 0.000 abstract description 4
- 102100023076 Protein Niban 1 Human genes 0.000 abstract description 4
- 102000052575 Proto-Oncogene Human genes 0.000 abstract description 4
- 108700020978 Proto-Oncogene Proteins 0.000 abstract description 4
- 102100020892 Uridine phosphorylase 1 Human genes 0.000 abstract description 4
- 230000009401 metastasis Effects 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 4
- 230000001737 promoting effect Effects 0.000 abstract description 4
- 102000004169 proteins and genes Human genes 0.000 abstract description 4
- 230000009545 invasion Effects 0.000 abstract description 3
- 230000007246 mechanism Effects 0.000 abstract description 3
- 238000013508 migration Methods 0.000 abstract description 3
- 230000009471 action Effects 0.000 abstract description 2
- 230000006907 apoptotic process Effects 0.000 abstract description 2
- 230000005012 migration Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 15
- 230000002018 overexpression Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 7
- 102000040945 Transcription factor Human genes 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 230000030279 gene silencing Effects 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- 230000007705 epithelial mesenchymal transition Effects 0.000 description 3
- 230000004568 DNA-binding Effects 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 102000055120 MEF2 Transcription Factors Human genes 0.000 description 2
- 108010018650 MEF2 Transcription Factors Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 2
- 108010012581 phenylalanylglutamate Proteins 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- RXTBLQVXNIECFP-FXQIFTODSA-N Ala-Gln-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O RXTBLQVXNIECFP-FXQIFTODSA-N 0.000 description 1
- UCDOXFBTMLKASE-HERUPUMHSA-N Ala-Ser-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N UCDOXFBTMLKASE-HERUPUMHSA-N 0.000 description 1
- NABSCJGZKWSNHX-RCWTZXSCSA-N Arg-Arg-Thr Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H]([C@H](O)C)C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N NABSCJGZKWSNHX-RCWTZXSCSA-N 0.000 description 1
- XVLLUZMFSAYKJV-GUBZILKMSA-N Arg-Asp-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XVLLUZMFSAYKJV-GUBZILKMSA-N 0.000 description 1
- KMSHNDWHPWXPEC-BQBZGAKWSA-N Arg-Asp-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KMSHNDWHPWXPEC-BQBZGAKWSA-N 0.000 description 1
- HPKSHFSEXICTLI-CIUDSAMLSA-N Arg-Glu-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O HPKSHFSEXICTLI-CIUDSAMLSA-N 0.000 description 1
- NYZGVTGOMPHSJW-CIUDSAMLSA-N Arg-Glu-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N NYZGVTGOMPHSJW-CIUDSAMLSA-N 0.000 description 1
- SKTGPBFTMNLIHQ-KKUMJFAQSA-N Arg-Glu-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SKTGPBFTMNLIHQ-KKUMJFAQSA-N 0.000 description 1
- VEAIMHJZTIDCIH-KKUMJFAQSA-N Arg-Phe-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O VEAIMHJZTIDCIH-KKUMJFAQSA-N 0.000 description 1
- ISJWBVIYRBAXEB-CIUDSAMLSA-N Arg-Ser-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O ISJWBVIYRBAXEB-CIUDSAMLSA-N 0.000 description 1
- BRCVLJZIIFBSPF-ZLUOBGJFSA-N Asn-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)N)N BRCVLJZIIFBSPF-ZLUOBGJFSA-N 0.000 description 1
- FAEIQWHBRBWUBN-FXQIFTODSA-N Asp-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N FAEIQWHBRBWUBN-FXQIFTODSA-N 0.000 description 1
- RSMIHCFQDCVVBR-CIUDSAMLSA-N Asp-Gln-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CCCNC(N)=N RSMIHCFQDCVVBR-CIUDSAMLSA-N 0.000 description 1
- DWOGMPWRQQWPPF-GUBZILKMSA-N Asp-Leu-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O DWOGMPWRQQWPPF-GUBZILKMSA-N 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 102000002664 Core Binding Factor Alpha 2 Subunit Human genes 0.000 description 1
- 108010043471 Core Binding Factor Alpha 2 Subunit Proteins 0.000 description 1
- 102000006990 Core Binding Factors Human genes 0.000 description 1
- 108010072732 Core Binding Factors Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- NUMFTVCBONFQIQ-DRZSPHRISA-N Gln-Ala-Phe Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O NUMFTVCBONFQIQ-DRZSPHRISA-N 0.000 description 1
- WOACHWLUOFZLGJ-GUBZILKMSA-N Gln-Arg-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O WOACHWLUOFZLGJ-GUBZILKMSA-N 0.000 description 1
- MFJAPSYJQJCQDN-BQBZGAKWSA-N Gln-Gly-Glu Chemical compound NC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O MFJAPSYJQJCQDN-BQBZGAKWSA-N 0.000 description 1
- FHPXTPQBODWBIY-CIUDSAMLSA-N Glu-Ala-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FHPXTPQBODWBIY-CIUDSAMLSA-N 0.000 description 1
- RCCDHXSRMWCOOY-GUBZILKMSA-N Glu-Arg-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O RCCDHXSRMWCOOY-GUBZILKMSA-N 0.000 description 1
- YYOBUPFZLKQUAX-FXQIFTODSA-N Glu-Asn-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YYOBUPFZLKQUAX-FXQIFTODSA-N 0.000 description 1
- RDPOETHPAQEGDP-ACZMJKKPSA-N Glu-Asp-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O RDPOETHPAQEGDP-ACZMJKKPSA-N 0.000 description 1
- QPRZKNOOOBWXSU-CIUDSAMLSA-N Glu-Asp-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N QPRZKNOOOBWXSU-CIUDSAMLSA-N 0.000 description 1
- ILGFBUGLBSAQQB-GUBZILKMSA-N Glu-Glu-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ILGFBUGLBSAQQB-GUBZILKMSA-N 0.000 description 1
- XTZDZAXYPDISRR-MNXVOIDGSA-N Glu-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N XTZDZAXYPDISRR-MNXVOIDGSA-N 0.000 description 1
- HBMRTXJZQDVRFT-DZKIICNBSA-N Glu-Tyr-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O HBMRTXJZQDVRFT-DZKIICNBSA-N 0.000 description 1
- OQQKUTVULYLCDG-ONGXEEELSA-N Gly-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)CN)C(O)=O OQQKUTVULYLCDG-ONGXEEELSA-N 0.000 description 1
- FKESCSGWBPUTPN-FOHZUACHSA-N Gly-Thr-Asn Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O FKESCSGWBPUTPN-FOHZUACHSA-N 0.000 description 1
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- DPTBVFUDCPINIP-JURCDPSOSA-N Ile-Ala-Phe Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 DPTBVFUDCPINIP-JURCDPSOSA-N 0.000 description 1
- VBGCPJBKUXRYDA-DSYPUSFNSA-N Ile-Trp-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CCCCN)C(=O)O)N VBGCPJBKUXRYDA-DSYPUSFNSA-N 0.000 description 1
- MJOZZTKJZQFKDK-GUBZILKMSA-N Leu-Ala-Gln Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(N)=O MJOZZTKJZQFKDK-GUBZILKMSA-N 0.000 description 1
- OIARJGNVARWKFP-YUMQZZPRSA-N Leu-Asn-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O OIARJGNVARWKFP-YUMQZZPRSA-N 0.000 description 1
- ULXYQAJWJGLCNR-YUMQZZPRSA-N Leu-Asp-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O ULXYQAJWJGLCNR-YUMQZZPRSA-N 0.000 description 1
- VPKIQULSKFVCSM-SRVKXCTJSA-N Leu-Gln-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VPKIQULSKFVCSM-SRVKXCTJSA-N 0.000 description 1
- LAGPXKYZCCTSGQ-JYJNAYRXSA-N Leu-Glu-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O LAGPXKYZCCTSGQ-JYJNAYRXSA-N 0.000 description 1
- ZRHDPZAAWLXXIR-SRVKXCTJSA-N Leu-Lys-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O ZRHDPZAAWLXXIR-SRVKXCTJSA-N 0.000 description 1
- WRODMZBHNNPRLN-SRVKXCTJSA-N Lys-Leu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O WRODMZBHNNPRLN-SRVKXCTJSA-N 0.000 description 1
- PLDJDCJLRCYPJB-VOAKCMCISA-N Lys-Lys-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PLDJDCJLRCYPJB-VOAKCMCISA-N 0.000 description 1
- STLBOMUOQNIALW-BQBZGAKWSA-N Met-Gly-Cys Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@@H](CS)C(O)=O STLBOMUOQNIALW-BQBZGAKWSA-N 0.000 description 1
- PHKBGZKVOJCIMZ-SRVKXCTJSA-N Met-Pro-Arg Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PHKBGZKVOJCIMZ-SRVKXCTJSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- OXKJSGGTHFMGDT-UFYCRDLUSA-N Phe-Phe-Arg Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C1=CC=CC=C1 OXKJSGGTHFMGDT-UFYCRDLUSA-N 0.000 description 1
- WKLMCMXFMQEKCX-SLFFLAALSA-N Phe-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O WKLMCMXFMQEKCX-SLFFLAALSA-N 0.000 description 1
- AJCRQOHDLCBHFA-SRVKXCTJSA-N Pro-His-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(O)=O AJCRQOHDLCBHFA-SRVKXCTJSA-N 0.000 description 1
- ZJXXCGZFYQQETF-CYDGBPFRSA-N Pro-Met-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1 ZJXXCGZFYQQETF-CYDGBPFRSA-N 0.000 description 1
- GOMUXSCOIWIJFP-GUBZILKMSA-N Pro-Ser-Arg Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O GOMUXSCOIWIJFP-GUBZILKMSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- GJFYFGOEWLDQGW-GUBZILKMSA-N Ser-Leu-Gln Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CO)N GJFYFGOEWLDQGW-GUBZILKMSA-N 0.000 description 1
- WGDYNRCOQRERLZ-KKUMJFAQSA-N Ser-Lys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)N WGDYNRCOQRERLZ-KKUMJFAQSA-N 0.000 description 1
- GZYNMZQXFRWDFH-YTWAJWBKSA-N Thr-Arg-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N)O GZYNMZQXFRWDFH-YTWAJWBKSA-N 0.000 description 1
- HLDFBNPSURDYEN-VHWLVUOQSA-N Trp-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N HLDFBNPSURDYEN-VHWLVUOQSA-N 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- ZZDYJFVIKVSUFA-WLTAIBSBSA-N Tyr-Thr-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O ZZDYJFVIKVSUFA-WLTAIBSBSA-N 0.000 description 1
- SLLKXDSRVAOREO-KZVJFYERSA-N Val-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N)O SLLKXDSRVAOREO-KZVJFYERSA-N 0.000 description 1
- XJFXZQKJQGYFMM-GUBZILKMSA-N Val-Cys-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)O)N XJFXZQKJQGYFMM-GUBZILKMSA-N 0.000 description 1
- JSOXWWFKRJKTMT-WOPDTQHZSA-N Val-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N JSOXWWFKRJKTMT-WOPDTQHZSA-N 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 108010087924 alanylproline Proteins 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 108010013835 arginine glutamate Proteins 0.000 description 1
- 108010018691 arginyl-threonyl-arginine Proteins 0.000 description 1
- 108010062796 arginyllysine Proteins 0.000 description 1
- 108010060035 arginylproline Proteins 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000005773 cancer-related death Effects 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000011748 cell maturation Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000008995 epigenetic change Effects 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 108010080575 glutamyl-aspartyl-alanine Proteins 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 108010037850 glycylvaline Proteins 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 108010064235 lysylglycine Proteins 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000011164 ossification Effects 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 201000002523 pancreas lymphoma Diseases 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 108010048818 seryl-histidine Proteins 0.000 description 1
- 230000001743 silencing effect Effects 0.000 description 1
- 108010061238 threonyl-glycine Proteins 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses application of shRNA for CBFbeta in preparing a medicine for treating colorectal cancer, wherein the sequence of the CBFbeta is shown as SEQ ID No. 1. The invention discovers that CBF beta can promote the proliferation, migration and invasion of colorectal cancer cells and inhibit apoptosis, and the expression of CBF beta is increased in clinical colorectal cancer, thereby playing a promoting role in the occurrence and development process of colorectal cancer. The action mechanism is that CBF beta forms a transcription complex related protein with RUNX2, and the transcription of protooncogenes OPN, FAM129A and UPP1 is activated, so that the growth and the metastasis of colorectal cancer are promoted. Therefore, CBF beta can be used as an important target point in early colorectal cancer discovery and treatment, the expression of CBF beta is silenced, and the growth of colorectal cancer cells HCT116 in mouse xenograft tumors can be inhibited.
Description
Technical Field
The invention relates to application of shRNA aiming at CBFbeta in preparing a medicine for treating colorectal cancer, belonging to the technical field of biological genes.
Background
Colorectal cancer (CRC) is one of the most common types of cancer worldwide, second-ranked in the incidence of cancer in adult females, third-ranked in males, and fourth-ranked in the mortality of cancer worldwide. Liver metastasis of colorectal cancer is a leading cause of colorectal cancer-related death. Previous studies have shown that genetic and epigenetic changes in patients during the onset of colorectal cancer play a key role in their pathogenesis and progression. The role of transcription factors in this process is not negligible. For example, the dysregulation of beta-catenin leads to the modification of tumor-associated gene expression and the disturbance of intracellular regulatory networks, thereby promoting the development of colorectal cancer. High expression of cardiomyocyte enhancer factor 2D (MEF2D) was associated with poor metastasis process and prognosis in colorectal cancer patients, MEF2D could activate EZEB1 transcription, promoting tumor cell invasion and Epithelial Mesenchymal Transition (EMT). Therefore, the study of the mechanism of transcription factor dysregulation is crucial for the treatment of colorectal cancer.
The core binding factor (CBF β) is a heterodimeric transcription factor consisting of a DNA-binding alpha subunit (also known as Runt-related transcription factor, RUNX) and a non-DNA-binding beta subunit (CBF β). The RUNX family has three members, RUNX1, RUNX2 and RUNX 3. After dimerization, the CBF β -RUNX heterodimer complex undergoes structural changes, thereby achieving high affinity and stability for binding to DNA. The complex regulates the expression of genes of interest involved in a variety of physiological processes, such as genes involved in hematopoietic cell maturation and bone formation. There is evidence that CBF β is critical for the growth of prostate and ovarian cancer cells and for the invasion of breast cancer cells. The RUNX genes play different roles in different types of cancer, and they can function as both oncogenes and cancer suppressor genes. The carcinogenic effect of RUNX2 was demonstrated in osteosarcomas, pancreatic cancers and lymphomas. RUNX2 was identified as an epigenetic regulator of EMT by comprehensive multiomic analysis of colon cancer cell lines. Downregulation of RUNX2 in colorectal cancer cells by small interfering rna (sirna) significantly reduced tumor cell proliferation and migration. CBF beta and RUNX2 are closely related to the functions in the development of colorectal cancer.
Disclosure of Invention
The invention aims to provide application of shRNA aiming at CBFbeta in preparing a medicine for treating colorectal cancer.
The technical scheme adopted by the invention is as follows: application of shRNA aiming at CBF beta in preparing a medicine for treating colorectal cancer, wherein the sequence of the CBF beta is shown as SEQ ID No. 1.
The invention discovers that CBF beta can promote the proliferation, migration and invasion of colorectal cancer cells and inhibit apoptosis, and the expression of CBF beta is increased in clinical colorectal cancer, thereby playing a promoting role in the occurrence and development process of colorectal cancer. The action mechanism is that CBF beta and RUNX2 form transcription complex related protein, and the transcription of protooncogenes OPN, FAM129A and UPP1 is activated, so that the growth and the metastasis of colorectal cancer are promoted.
Therefore, CBF beta can be used as an important target point in early discovery and treatment of colorectal cancer, the expression of CBF beta is silenced, and the growth of a colorectal cancer cell HCT116 in a mouse xenograft tumor can be inhibited.
Drawings
FIG. 1, amino acid sequence of CBFbeta.
FIG. 2, CBF β overexpression plasmid.
Figure 3 overexpression and silencing effect against CBF β in HCT116 cells.
FIG. 4, the effect of CBF β and RUNX2 on the transcript level of downstream target genes.
FIG. 5, effects of CBF β overexpression and silencing on cell growth proliferation capacity.
Figure 6, effect of CBF β overexpression and silencing on mouse transplanted tumor growth.
FIG. 7, expression of CBF β in CRC patient sample sections.
Detailed Description
To further illustrate the technical means and effects of the present invention adopted to achieve the predetermined objects, the following detailed description of the embodiments, structures, characteristics and effects according to the present invention will be given with reference to the preferred embodiments.
S1, constructing CBF beta expression plasmid (shown in figure 2) according to the amino acid sequence (shown in figure 1) of CBF beta.
S2, infecting the HCT116 cell line by using the over-expression lentivirus vector and shRNA lentivirus vector aiming at the CBFbeta, and establishing a colorectal cancer cell line and a control cell line which stably over-express the CBFbeta and silence the CBFbeta.
As shown in fig. 3, although CBF β is normally expressed in shcontrol, the expression of CBF β in shCBF β is significantly reduced, and the purpose of interfering with the expression of CBF β is achieved. CBF beta in the control is normally expressed, but CBF beta expression in a CBF beta overexpression cell line is obviously increased, and the purpose of over-expressing CBF beta is achieved. The expression level of the reference gene GAPDH is consistent in 4 cell lines.
S3, detecting the influence of the over-expressed CBF beta on the transcription pair of the downstream target gene by Western blot. As a result, as shown in FIG. 4, CBF β has an upregulation effect on protooncogenes OPN, FAM129A and UPP1, and the upregulation effect was suppressed after interference with RUNX 2.
S4, FIG. 5 shows that silencing CBF β inhibits the growth proliferation ability of HCT116, while over-expressing CBF β promotes the growth proliferation ability of HCT 116.
S5, tumor-bearing mice show that silencing CBF beta inhibits the growth of the colorectal cancer cell HCT116 xenografted tumor in the mice, as shown in figure 6, the tumor body of the shCBF beta group of the experimental group is smaller than that of the shcontrol group, and the over-expression of CBF beta promotes the growth of the colorectal cancer cell HCT116 xenografted tumor in the mice.
The invention utilizes a CBF beta overexpression viral vector to construct a CBF beta overexpression HCT116 cell line. Overexpression of CBF β up-regulates transcription of downstream proto-oncogenes. CBF beta and RUNX2 form a complex related protein, and the complex related protein is combined with promoter sequences of OPN, FAM129A, UPP1 and the like to promote transcription, so that the development of colorectal cancer is promoted. Therefore, the invention provides a new idea and a new target point for treating the colorectal cancer.
Although the present invention has been described with reference to the preferred embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the present invention.
Sequence listing
<110> Nanjing university
<120> application of shRNA aiming at CBFbeta in preparing medicine for treating colorectal cancer
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 182
<212> PRT
<213> Homo sapiens
<400> 1
Met Pro Arg Val Val Pro Asp Gln Arg Ser Lys Phe Glu Asn Glu Glu
1 5 10 15
Phe Phe Arg Lys Leu Ser Arg Glu Cys Glu Ile Lys Tyr Thr Gly Phe
20 25 30
Arg Asp Arg Pro His Glu Glu Arg Gln Ala Arg Phe Gln Asn Ala Cys
35 40 45
Arg Asp Gly Arg Ser Glu Ile Ala Phe Val Ala Thr Gly Thr Asn Leu
50 55 60
Ser Leu Gln Phe Phe Pro Ala Ser Trp Gln Gly Glu Gln Arg Gln Thr
65 70 75 80
Pro Ser Arg Glu Tyr Val Asp Leu Glu Arg Glu Ala Gly Lys Val Tyr
85 90 95
Leu Lys Ala Pro Met Ile Leu Asn Gly Val Cys Val Ile Trp Lys Gly
100 105 110
Trp Ile Asp Leu Gln Arg Leu Asp Gly Met Gly Cys Leu Glu Phe Asp
115 120 125
Glu Glu Arg Ala Gln Gln Glu Asp Ala Leu Ala Gln Gln Ala Phe Glu
130 135 140
Glu Ala Arg Arg Arg Thr Arg Glu Phe Glu Asp Arg Asp Arg Ser His
145 150 155 160
Arg Glu Glu Met Glu Val Arg Val Ser Gln Leu Leu Ala Val Thr Gly
165 170 175
Lys Lys Thr Thr Arg Pro
180
Claims (1)
1. Application of shRNA aiming at CBFbeta in preparing a medicine for treating colorectal cancer, wherein the sequence of the CBFbeta is shown as SEQ ID No. 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210516955.7A CN114748498A (en) | 2022-05-13 | 2022-05-13 | Application of shRNA aiming at CBFbeta in preparation of colorectal cancer treatment drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210516955.7A CN114748498A (en) | 2022-05-13 | 2022-05-13 | Application of shRNA aiming at CBFbeta in preparation of colorectal cancer treatment drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114748498A true CN114748498A (en) | 2022-07-15 |
Family
ID=82334161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210516955.7A Pending CN114748498A (en) | 2022-05-13 | 2022-05-13 | Application of shRNA aiming at CBFbeta in preparation of colorectal cancer treatment drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114748498A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101932724A (en) * | 2007-10-05 | 2010-12-29 | 环太平洋生物技术有限公司 | The hyperplasia label and the prognosis of gastrointestinal cancer |
| US20170233375A1 (en) * | 2014-08-13 | 2017-08-17 | University Of Virginia Patent Foundation | Cancer therapeutics |
| CN109789158A (en) * | 2016-07-29 | 2019-05-21 | 国立大学法人京都大学 | RUNX inhibitor |
| CN112601583A (en) * | 2018-03-07 | 2021-04-02 | 波赛达治疗公司 | CARTyrin compositions and methods of use |
-
2022
- 2022-05-13 CN CN202210516955.7A patent/CN114748498A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101932724A (en) * | 2007-10-05 | 2010-12-29 | 环太平洋生物技术有限公司 | The hyperplasia label and the prognosis of gastrointestinal cancer |
| US20170233375A1 (en) * | 2014-08-13 | 2017-08-17 | University Of Virginia Patent Foundation | Cancer therapeutics |
| CN109789158A (en) * | 2016-07-29 | 2019-05-21 | 国立大学法人京都大学 | RUNX inhibitor |
| CN112601583A (en) * | 2018-03-07 | 2021-04-02 | 波赛达治疗公司 | CARTyrin compositions and methods of use |
Non-Patent Citations (7)
| Title |
|---|
| CHEN WANG, 等: "CBF beta promotes colorectal cancer progression through transcriptionally activating OPN, FAM129A, and UPP1 in a RUNX2-dependent manner", CELL DEATH & DIFFERENTIATION, vol. 28, pages 6176 * |
| YOSHIKAVA R, 等: "core-binding factor subunit beta", GENEBANK DATABASE, pages 001291957 * |
| 张海元;等: "结直肠癌细胞系中Runx3及Runx2基因表达分析", 长江大学学报(自科版)医学卷, no. 02, pages 1 - 3 * |
| 熊加秀;等: "敲低Runt相关转录因子2(Runx2)表达抑制结肠癌细胞生长和迁移", 细胞与分子免疫学杂志, vol. 32, no. 07, pages 950 - 953 * |
| 章台柳: "南京大学团队：CBFβ 促进结直肠癌进展", Retrieved from the Internet <URL:https://www.chinagut.cn/papers/read/1084308619> * |
| 赵然, 等: "核酸药物及其给药系统用于炎症性肠病治疗的研究进展", 药学进展, vol. 37, no. 11, pages 574 - 579 * |
| 郭宇: "共转录因子CBFβ在结直肠癌中的功能研究", 中国优秀硕士学位论文全文数据库医药卫生科技辑, no. 06, pages 072 - 169 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Jiang et al. | HCP5 is a SMAD3-responsive long non-coding RNA that promotes lung adenocarcinoma metastasis via miR-203/SNAI axis | |
| Liu et al. | MiR-141 suppresses the migration and invasion of HCC cells by targeting Tiam1 | |
| Meng et al. | shRNA-mediated knockdown of Bmi-1 inhibit lung adenocarcinoma cell migration and metastasis | |
| Peacock et al. | Vav3 enhances androgen receptor splice variant activity and is critical for castration-resistant prostate cancer growth and survival | |
| Zhu et al. | TRAF6 promotes the progression and growth of colorectal cancer through nuclear shuttle regulation NF-kB/c-jun signaling pathway | |
| Lacoste et al. | Iodide transporter NIS regulates cancer cell motility and invasiveness by interacting with the Rho guanine nucleotide exchange factor LARG | |
| Liu et al. | Long non-coding RNA FLVCR1-AS1 sponges miR-155 to promote the tumorigenesis of gastric cancer by targeting c-Myc | |
| Yoon et al. | Thymosin β4 expression correlates with lymph node metastasis through hypoxia inducible factor-α induction in breast cancer | |
| Cao et al. | HIF-2α regulates CDCP1 to promote PKCδ-mediated migration in hepatocellular carcinoma | |
| JP7376873B2 (en) | Cancer-promoting factor expression inhibitor, method for screening its active ingredient, expression cassette useful for the method, diagnostic agent, and diagnostic method | |
| Zhou et al. | MicroRNA-638 inhibits cell growth and tubule formation by suppressing VEGFA expression in human Ewing sarcoma cells | |
| Zhu et al. | MiR-346 suppresses cell proliferation through SMYD3 dependent approach in hepatocellular carcinoma | |
| Dimri et al. | PLK1 inhibition down-regulates polycomb group protein BMI1 via modulation of the miR-200c/141 cluster | |
| WO2020093573A1 (en) | Application of ephrina1 protein in preparation of drugs for inhibiting tumor cell invasion and metastasis | |
| Chen et al. | LncRNA LINC00313 knockdown inhibits tumorigenesis and metastasis in human osteosarcoma by upregulating FOSL2 through sponging miR-342-3p | |
| US20200326343A1 (en) | Gene and its expression product promoting the occurrence and development of cancer and application | |
| Zhang et al. | Regulation of docetaxel chemosensitivity by NR2F6 in breast cancer | |
| Gao et al. | Long non-coding RNA linc-cdh4-2 inhibits the migration and invasion of HCC cells by targeting R-cadherin pathway | |
| Gozo et al. | FOXC2 augments tumor propagation and metastasis in osteosarcoma | |
| Wu et al. | METTL13 facilitates cell growth and metastasis in gastric cancer via an eEF1A/HN1L positive feedback circuit | |
| CN114748498A (en) | Application of shRNA aiming at CBFbeta in preparation of colorectal cancer treatment drug | |
| Zheng et al. | The TGFβ-induced long non-coding RNA TBULC promotes the invasion and migration of non-small cell lung cancer cells and indicates poor prognosis | |
| Ren et al. | Decreased lncRNA, TINCR, promotes growth of colorectal carcinoma through upregulating microRNA-31 | |
| Sanada et al. | Heterogeneous expression and role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in small cell lung cancer | |
| Zou et al. | Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220715 |