CN117089619A - 一种用于诊断结肠癌的生物标志物及其应用 - Google Patents
一种用于诊断结肠癌的生物标志物及其应用 Download PDFInfo
- Publication number
- CN117089619A CN117089619A CN202311207386.9A CN202311207386A CN117089619A CN 117089619 A CN117089619 A CN 117089619A CN 202311207386 A CN202311207386 A CN 202311207386A CN 117089619 A CN117089619 A CN 117089619A
- Authority
- CN
- China
- Prior art keywords
- colon cancer
- linc00667
- gene
- biomarker
- seq
- 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 64
- 208000029742 colonic neoplasm Diseases 0.000 title claims abstract description 63
- 239000000090 biomarker Substances 0.000 title claims abstract description 18
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 44
- 230000014509 gene expression Effects 0.000 claims abstract description 33
- 239000003112 inhibitor Substances 0.000 claims abstract description 11
- 239000002773 nucleotide Substances 0.000 claims abstract description 10
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 10
- 238000001514 detection method Methods 0.000 claims abstract description 6
- 239000004055 small Interfering RNA Substances 0.000 claims description 23
- 241000713666 Lentivirus Species 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 8
- -1 ZFN Proteins 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 108091030071 RNAI Proteins 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000009368 gene silencing by RNA Effects 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 5
- 230000006801 homologous recombination Effects 0.000 claims description 4
- 238000002744 homologous recombination Methods 0.000 claims description 4
- 239000000080 wetting agent Substances 0.000 claims description 4
- 108091027544 Subgenomic mRNA Proteins 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 238000003745 diagnosis Methods 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000945 filler Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 238000001179 sorption measurement Methods 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 238000010521 absorption reaction Methods 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000003623 enhancer Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000010459 TALEN Methods 0.000 claims 1
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 210000004027 cell Anatomy 0.000 description 41
- 108091046869 Telomeric non-coding RNA Proteins 0.000 description 16
- 206010028980 Neoplasm Diseases 0.000 description 14
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002452 interceptive effect Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000003753 real-time PCR Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000011729 BALB/c nude mouse Methods 0.000 description 3
- 108091033409 CRISPR Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 238000012404 In vitro experiment Methods 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108020005198 Long Noncoding RNA Proteins 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 2
- 230000006718 epigenetic regulation Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- DBTMGCOVALSLOR-DEVYUCJPSA-N (2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](CO)O[C@H](O)[C@@H]2O)O)O[C@H](CO)[C@H]1O DBTMGCOVALSLOR-DEVYUCJPSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
- 108020005004 Guide RNA Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 239000005717 Laminarin Substances 0.000 description 1
- 229920001543 Laminarin Polymers 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 230000007022 RNA scission Effects 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 238000010818 SYBR green PCR Master Mix Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000004791 biological behavior Effects 0.000 description 1
- 230000007321 biological mechanism Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000010362 genome editing Methods 0.000 description 1
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 230000006780 non-homologous end joining Effects 0.000 description 1
- 230000025308 nuclear transport Effects 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008844 regulatory mechanism Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000010863 targeted diagnosis Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Abstract
本发明公开了一种用于诊断结肠癌的生物标志物及其应用,所述生物标志物为基因LINC00667,核苷酸序列如SEQ ID NO.1所示。本发明揭示了基因LINC00667在结肠癌细胞中的重要角色,其表达水平在结肠癌细胞中显著升高,因此可以作为结肠癌检测的有效生物标志物。同时本发明提出了一种以基因LINC00667为靶点,制备功能性表达抑制剂来预防或治疗结肠癌的方案。这一发现为结肠癌的治疗提供了新的策略和方向,具有极高的临床应用价值,有望为结肠癌患者带来更好的治疗效果。
Description
技术领域
本发明属于生物医药技术领域,具体涉及一种用于诊断结肠癌的生物标志物及其应用。
背景技术
结肠癌是一种常见的恶性肿瘤,其发病率和死亡率均呈上升趋势。如何针对结肠癌的发病特点制定针对性的诊疗手段,提高疾病治疗预后,是目前迫切需要解决的问题。
最近的研究表明,在哺乳动物基因组中,只有不到2%的基因能够编码蛋白质,而大约98%的基因都编码成非编码RNA。这些非编码RNA根据其长度,分为两类:一类是非编码小RNA(sncRNA),其转录长度少于200个核苷酸;另一类是长链非编码RNA(lncRNA),被广泛的定义为转录长度超过200个核苷酸并且没有表观编码能力的RNA。lncRNA具有复杂的二级结构、三级结构,能够与蛋白质、RNA、DNA结合,从而为miRNA、mRNA、蛋白质或者其复合物进行相互作用提供了平台。越来越多的证据显示,lncRNA在基因转录、转录后调控、RNA剪切、翻译、表观遗传调控等过程中都发挥着重要作用,并与结肠癌的生物学行为关系密切。
lncRNA的主要特点包括:(1)lncRNA通常较长,具有mRNA样结构,经过剪接,具有polyA尾巴与启动子结构,分化过程中有动态的表达与不同的剪接方式;(2)有组织特异性与时空特异性,不同组织之间的lncRNA表达量不同,同一组织或器官在不同生长阶段,lncRNA表达量也会变化;(3)调控多样性:lncRNA可从染色质重塑、转录调控及转录后加工等多种层面实现对基因表达的调控;(4)序列上保守性较低,只有约12%的lncRNA可在人类之外的其它生物中找到;在肿瘤与其他疾病中有特征性的表达方式。由于lncRNA参与X染色体沉默、染色体修饰和基因组修饰、转录激活、转录干扰、核内运输等过程,因此lncRNA是临床医学研究中的热点分子。其可以通过不同的分子生物学机制调控编码基因的表达,参与疾病相关的信号通路,从而对疾病的发生、发展及治疗有重要作用。大量的研究显示肿瘤细胞中某些特定lncRNA的表达水平发生异常改变,这种异常表达的lncRNA能够作为肿瘤诊断的分子标记物和潜在的药物靶点。目前lncRNA还处于起步阶段,且只有少数与癌症相关的lncRNA被报道出来。研究与结肠癌相关的lncRNA对于实现有效预防和治疗结肠癌,以及精准医疗具有重要的意义。
LINC00667,坐落在18号染色体,产生一个长度为3979bp的长非编码RNA。这个基因在转录的表观遗传调控中发挥重要作用,作为一个新近被发现的在结肠癌中异常表达的lncRNA,其调控机制及病理作用尚未被详细报道。
发明内容
针对现有技术的不足,本发明提供一种用于诊断结肠癌的生物标志物及其应用,揭示了基因LINC00667在结肠癌发生发展中的重要作用,并为其治疗提供了新的可能方案和药物开发方向。
本发明是通过以下技术方案实现的:
一种用于诊断结肠癌的生物标志物,其特征在于,所述生物标志物为基因LINC00667,核苷酸序列如SEQ ID NO.1所示。
检测上述的生物标志物的产品在制备用于诊断结肠癌的试剂盒中的应用。
优选地,所述试剂盒通过检测受试者样本组织中基因LINC00667的表达水平进行诊断,罹患结肠癌的患者的样本中基因LINC00667的表达水平显著上调。
优选地,所述产品为检测试剂,所述检测试剂包括引物对,所述引物对的核苷酸序列如SEQ ID NO.2-3所示。
上述的生物标志物的功能性表达抑制剂在制备治疗结肠癌的药物中的应用。
优选地,所述功能性表达抑制剂为shRNA慢病毒、RNAi、sgRNA、ZFN、TALEN元件或同源重组载体。
优选地,所述shRNA慢病毒的核苷酸序列如SEQ ID NO.5所示。
一种预防或治疗结肠癌的药物组合物,包括上述的功能性表达抑制剂,以及药学上可接受的载体。
优选地,所述载体包括稀释剂、填充剂、粘合剂、湿润剂、崩解剂、吸收促进剂、表面活性剂、吸附载体和润滑剂中的一种或多种。
优选地,所述药物组合物为片剂、胶囊剂、散剂、丸剂、颗粒剂、溶液剂、混悬剂、糖浆剂、注射剂、栓剂、吸入剂或喷雾剂。
本发明的有益效果如下:
本发明揭示了基因LINC00667在结肠癌细胞中的重要角色,其表达水平在结肠癌细胞中显著升高,因此可以作为结肠癌检测的有效生物标志物。为了深入研究基因LINC00667在结肠癌发生发展中的作用,本发明建立了LINC00667在体外结肠癌细胞模型中的敲除研究,以及在体内原位移植瘤模型中的敲除研究。这些实验结果表明,基因LINC00667在结肠癌细胞中具有显著的增殖抑制作用,并能明显促进结肠癌细胞的凋亡。因此,敲除LINC00667可能成为预防或治疗结肠癌的一种有效手段。基于以上发现,本发明提出了一种以基因LINC00667为靶点,制备功能性表达抑制剂来预防或治疗结肠癌的方案。这一发现为结肠癌的治疗提供了新的策略和方向,具有极高的临床应用价值,有望为结肠癌患者带来更好的治疗效果。
附图说明
图1为实施例1中荧光定量PCR检测基因LINC00667在结肠癌细胞LoVo及SW480中的表达情况;
图2为实施例2中体外实验的细胞增殖图(A)和细胞划痕及迁移率图(B);
图3为实施例2中体内实验的肿瘤图(A)及肿瘤体积统计图(B)。
具体实施方式
下面结合附图与具体实施例对本发明做进一步详细说明。
若无特殊说明,以下实施例中所用的技术手段,均为本领域技术人员所熟知的常规手段,未注明具体条件的实验方法,均为本领域常规方法。
以下实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
以下实施例中所用实验动物为6周龄的BALB/c裸鼠,购自Gem pharma(中国南京)。
以下实施例中所用到的结直肠癌细胞株SW480、LoVo购自American Type CultureCollection(ATCC,USA)。
实施例1
本实施例选用LoVo、SW480细胞作为结肠癌细胞的代表进行实验,通过荧光定量PCR检测了结肠癌细胞LoVo和SW480中基因LINC00667的表达情况,具体如下:
1、应用Trizol试剂(Invitrogen,Carlsbad,USA)从细胞和组织样品中取总RNA。
(1)吸尽6孔板中结肠癌细胞LoVo,SW480的培养液,每孔加入1mL Trizol,使其覆盖细胞,再用吸管或加样器吹打3次,细胞应完全裂解,然后转移至离心管中。
(2)在装有裂解物的离心管中加入0.2mL的氯仿(1mL Trizol加入0.2mL氯仿),振荡器上充分振荡混匀20s,室温放置5min。12000rpm 4℃离心10min,然后吸取含总RNA的上层水相至一新的离心管中,每毫升Trizol约可吸取0.6mL上层水相。有机相和中间层含有DNA和蛋白质,应避免触及。
(3)加入和上层水相等体积的异丙醇,颠倒数次混匀,室温沉淀5min。12000rpm 4℃离心15min,在管底可见RNA沉淀。弃上清,按每毫升Trizol加入1mL75%乙醇,轻轻颠倒混匀,以清洗RNA沉淀。12000rpm 4℃离心2min,弃去液体,小心勿丢弃RNA沉淀。室温倒置晾干5~10min。
(4)溶解:加入适量DEPC处理水使RNA沉淀溶解。存放于-80℃。
2、应用M-MLV逆转录酶合成第一链cDNA。
3、在总体积为20μL的SYBR Green PCR Master Mix(Roche,Germany)中进行实时定量PCR(qPCR)。所有反应均一式两份进行。使用2-ΔΔCT法方法计算基因LINC00667的相对表达量。用于磷酸化AKT的PCR引物在Invitrogen合成。以GAPDH作为内参照。基因LINC00667的引物对序列具体如下:
上游引物(SEQ ID NO.2):5’-GTGGGTAGGAAACAGTCGGG-3’;
下游引物(SEQ ID NO.3):5’-CTCAAAGGTGGCCAAAAGCC-3’。
基因LINC00667,核苷酸序列如SEQ ID NO.1所示。
4、实验结果
如图1所示,基因LINC00667在结肠癌细胞中的表达明显上调,且在高侵袭性细胞LoVo中的表达量相对较高,而在低侵袭性细胞SW480中的表达量相对较低。
本实施例的实验结果表明,基因LINC00667在结肠癌细胞中的表达明显上调,因此可以作为检测结肠癌的一个有效指标。
实施例2
为了深入研究基因LINC00667在结肠癌预防和治疗中的作用,本实施例构建了体外LINC00667敲除结肠癌细胞模型和体内LINC00667敲除结肠癌原位移植瘤模型,以验证基因LINC00667的敲除是否能抑制结肠肿瘤的生长并促进癌细胞凋亡。具体如下:
1、体外实验
(1)将对数生长期的结直肠癌细胞LoVo和SW480置于6孔板中,分别转染LINC00667干扰慢病毒(LINC00667-shRNA)或NC-shRNA(均购自上海和元生物技术股份有限公司),LINC00667-shRNA的感染复数(MOI)为20,转染后24h更换培养基。转染48h后,加入1μg/mL嘌呤霉素进行筛选。qPCR检测LINC00667的表达以验证转染成功。
NC-shRNA(SEQ ID NO.4):5’-CCGGCAGATTAGTCTCAACTTGACTCTCGAGAGTCAAGTTGAGACTAATCTG TTTTTG-3’;
LINC00667-shRNA(SEQ ID NO.5):5’-CCGGTACATGTTTGGTAGAGAACTACTCGAGTAGTTCTCTACCAAACATGTA TTTTTG-3’。
(2)CCK-8实验
96孔板分别接种经转染LINC00667干扰慢病毒(LINC00667-shRNA)或NC-shRNA处理的LoVo细胞,密度分别为1.5×103细胞。在含10% FBS的DMEM培养基中,于37℃、5% CO2培养箱中培养24h、48h、72h。随后,在96孔板中加入10μL CCK-8(道进岛,日本)并培养1h。最后,使用酶标仪(BioTek,美国)在450nm下计数和分析细胞(BioTek,美国)。
(3)细胞划痕实验
将转染LINC00667干扰慢病毒(LINC00667-shRNA)或NC-shRNA处理的LoVo细胞(2×105细胞/孔)接种于6孔板,在37℃、5% CO2培养箱中培养。200μL移液管尖端从细胞单层产生浆液直到细胞融合达到90%。将脱落的细胞用PBS轻轻洗涤3次。用新鲜无血清培养基孵育24h后,倒置显微镜下观察创面形态。迁移率=[0~24h时创面宽度(WW)/0h时创面宽度(WW)]。
2、体内实验
6周龄的BALB/c裸鼠饲养在标准的12小时光/暗循环条件下。将5×106感染了shRNA慢病毒的LoVo细胞(LINC00667-shRNA)与空载干扰组(NC-shRNA)以及正常对照组(Control),分别注射到BALB/c裸鼠背部皮下。于种瘤后第7、14、28d测量肿瘤体积。肿瘤体积(mm3)通过长度(mm)×宽度(mm)×高度(mm)×1/2计算。所有三组裸鼠都成功成瘤,成瘤时间平均为10天。在成瘤后20天,对小鼠进行安乐处死,并取瘤称重。
3、实验结果
体外实验如图2中A所示,与空载干扰组(NC-shRNA)相比,感染了RNAi慢病毒的LoVo细胞(LINC00667-shRNA)其增殖能力明显受到抑制,细胞增殖活性显著减弱(**P<0.01)。同时,如图2中B所示,LINC00667的敲除也明显抑制了结肠癌细胞的迁移能力(**P<0.01)。
体内实验如图3所示,LINC00667干扰的转染病毒组(LINC00667-shRNA)的肿瘤体积明显低于空载干扰组(NC-shRNA)和正常对照组(Control)(**P<0.01),这表明敲除LINC00667能显著抑制结肠癌细胞的增殖能力。
本实施例的实验结果表明,敲除LINC00667能显著抑制结肠癌细胞的增殖能力,同时敲除LINC00667还能明显抑制结肠癌细胞的迁移能力。因此开发基因LINC00667的功能性表达抑制剂(如本实施例的shRNA慢病毒)可以用于制备预防或治疗结肠癌的药物。
据文献记载,除了shRNA慢病毒,还有多种技术手段可以实现抑制LINC00667的功能性表达,或者抑制LINC00667下游物质的功能性表达,从而起到抑制LINC00667用于预防或治疗结肠癌方面的作用。这些技术手段包括但不限于其他RNAi技术,例如通过其他siRNA抑制LINC00667的功能性表达;成簇规律间隔短回文重复(CRISPR/Cas9技术为代表)技术,使用一段序列特异性向导RNA分子(sgRNA)引导核酸内切酶到靶点处,从而完成基因组编辑;锌指核酸酶(ZFN)技术,通过加工改造ZFN的锌指DNA结合域,靶向定位于不同的DNA序列;转录激活样效应因子核酸酶(TALEN)技术,通过DNA识别模块将TALEN元件靶向特异性的DNA位点并结合,然后在FokI核酸酶的作用下完成特定位点的剪切,并借助于细胞内固有的同源定向修复(HDR)或非同源末端连接途径(NHEJ)修复过程完成特定序列的插入(或倒置)、删失及基因融合;以及利用同源重组载体敲除基因的技术,例如Cre/LoxP系统或来自酵母的FLP-frt系统,利用基因同源重组原理,用设计的同源片段替代靶基因片段,从而达到基因敲除的目的。
因此,本发明的目的在于研发一种LINC00667功能性表达抑制剂用于制备预防或治疗结肠癌的药物组合物。为实现这一目标,本发明提出使用针对LINC00667的RNAi、针对LINC00667的shRNA慢病毒、针对LINC00667的sgRNA(需配合CRRSPR/Cas9使用)、针对LINC00667的ZFN(需配合ZFN技术使用)、针对LINC00667的TALEN元件(需配合TALEN技术使用)以及针对LINC00667的同源重组载体(利用Cre/LoxP系统或来自酵母的FLP-frt系统)。此外,本发明建议在药物组合物中加入其他药类以及药学上可接受的载体,包括:稀释剂如乳糖、氯化钠、葡萄糖、尿素、淀粉和水等,填充剂如淀粉和蔗糖等,粘合剂如单糖浆、葡萄糖溶液、淀粉溶液、纤维素衍生物、藻酸盐、明胶和聚乙烯吡咯烷酮,湿润剂如甘油,崩解剂如干淀粉、海藻酸钠、海带多糖粉末、琼脂粉末、碳酸钙和碳酸氢钠,吸收促进剂如季铵化合物和十二烷基硫酸钠等,表面活性剂如聚氧化乙烯山梨聚糖脂肪酸酯、十二烷基硫酸钠、硬脂酸单甘油酯和十六烷醇等,致湿剂如甘油和淀粉等,吸附载体如淀粉、乳糖、斑脱土、硅胶和高岭土等,以及润滑剂如滑石粉、硬脂酸钙和镁、聚乙二醇和硼酸粉末等。
综上所述,本发明的研究结果表明,基因LINC00667在结肠癌的治疗和预防中具有重要作用。敲除LINC00667可以显著抑制结肠癌细胞的增殖能力,并促进其凋亡。此外,本发明的研究还为开发LINC00667功能性表达抑制剂用于制备预防或治疗结肠癌的药物组合物提供了重要依据。
以上实施例仅是本发明的一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都应当属于本发明的保护范围。
Claims (10)
1.一种用于诊断结肠癌的生物标志物,其特征在于,所述生物标志物为基因LINC00667,核苷酸序列如SEQ ID NO.1所示。
2.检测权利要求1所述的生物标志物的产品在制备用于诊断结肠癌的试剂盒中的应用。
3.根据权利要求2所述的应用,其特征在于,所述试剂盒通过检测受试者样本组织中基因LINC00667的表达水平进行诊断,罹患结肠癌的患者的样本中基因LINC00667的表达水平显著上调。
4.根据权利要求2所述的应用,其特征在于,所述产品为检测试剂,所述检测试剂包括引物对,所述引物对的核苷酸序列如SEQ ID NO.2-3所示。
5.权利要求1所述的生物标志物的功能性表达抑制剂在制备治疗结肠癌的药物中的应用。
6.根据权利要求5所述的应用,其特征在于,所述功能性表达抑制剂为shRNA慢病毒、RNAi、sgRNA、ZFN、TALEN元件或同源重组载体。
7.根据权利要求6所述的应用,其特征在于,所述shRNA慢病毒的核苷酸序列如SEQ IDNO.5所示。
8.一种预防或治疗结肠癌的药物组合物,其特征在于,包括权利要求6或7所述的功能性表达抑制剂,以及药学上可接受的载体。
9.根据权利要求8所述的药物组合物,其特征在于,所述载体包括稀释剂、填充剂、粘合剂、湿润剂、崩解剂、吸收促进剂、表面活性剂、吸附载体和润滑剂中的一种或多种。
10.根据权利要求8所述的药物组合物,其特征在于,所述药物组合物为片剂、胶囊剂、散剂、丸剂、颗粒剂、溶液剂、混悬剂、糖浆剂、注射剂、栓剂、吸入剂或喷雾剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311207386.9A CN117089619A (zh) | 2023-09-19 | 2023-09-19 | 一种用于诊断结肠癌的生物标志物及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202311207386.9A CN117089619A (zh) | 2023-09-19 | 2023-09-19 | 一种用于诊断结肠癌的生物标志物及其应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN117089619A true CN117089619A (zh) | 2023-11-21 |
Family
ID=88775113
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202311207386.9A Pending CN117089619A (zh) | 2023-09-19 | 2023-09-19 | 一种用于诊断结肠癌的生物标志物及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN117089619A (zh) |
-
2023
- 2023-09-19 CN CN202311207386.9A patent/CN117089619A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO2018169994A1 (en) | m6A mRNA MODIFICATION IN CANCER TREATMENT | |
AU2018333072B2 (en) | Methods for treating triple-negative breast cancer | |
CN108004322B (zh) | 一种lncRNA在诊断和/或治疗肺腺癌中的应用 | |
CN111317820B (zh) | 剪接因子prpf31抑制剂用于制备药物的用途 | |
US20110124712A1 (en) | Anti-cancer composition comprising microrna molecules | |
JP5933010B2 (ja) | 癌治療剤 | |
CN106906217B (zh) | 抑制Kdm6a基因表达的siRNA及其应用 | |
CN113476606B (zh) | Upk1a-as1抑制剂在制备抗肿瘤药物中的应用 | |
CN117089619A (zh) | 一种用于诊断结肠癌的生物标志物及其应用 | |
CN113564252B (zh) | 甲基化酶mettl3的新用途 | |
CN115054694A (zh) | Crept在治疗前列腺癌中的用途 | |
Ren et al. | PAPAS promotes differentiation of mammary epithelial cells and suppresses breast carcinogenesis | |
CN111020036B (zh) | 人circ-STXBP5L的用途及相关产品 | |
CN117467770A (zh) | 一种结肠癌诊断生物标志物及其应用 | |
CN112725436A (zh) | 一种人circMKLN1基因的用途及相关产品 | |
CN103667430B (zh) | 一种八聚核苷酸结合蛋白表达基因的用途及其相关药物 | |
CN103421884B (zh) | 人fzr1基因的用途及其相关药物 | |
CN112852965B (zh) | lnc-ZNF100-5功能性表达抑制剂在制备治疗乳腺癌的药物中的应用 | |
CN113967261B (zh) | Folr1抑制剂的应用和治疗肝癌药物混合物 | |
CN114306608B (zh) | 一类适应低氧或缺氧微环境的肿瘤的治疗靶点及其应用 | |
CN103656673B (zh) | 人ywhaq基因的用途及其相关药物 | |
CN115927611A (zh) | 一种乳腺癌的生物标志物及其应用 | |
WO2020246717A1 (ko) | Heres 발현 억제제를 포함하는 편평상피세포암 예방 또는 치료용 약학적 조성물 | |
Figueroa et al. | Xing Cheng1, Jin Xu2, Zhengran Yu1, Jinghui Xu1 and Houqing Long1 | |
CN117778574A (zh) | Mir937基因组拷贝数扩增在卵巢癌诊断和/或治疗中的应用 |
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 |