CN113584163A - Application of TBC1D3 and its family in preparing tumor diagnosis medicine and prognosis judgment medicine - Google Patents
Application of TBC1D3 and its family in preparing tumor diagnosis medicine and prognosis judgment medicine Download PDFInfo
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Abstract
The invention provides application of TBC1D3 and a family thereof in preparation of tumor diagnosis drugs and prognosis judgment drugs, belonging to the technical field of biological medicines. The invention finds that the expression of TBC1D3 and the family gene thereof in the renal clear cell carcinoma tissue is obviously higher than that of a paracancer normal tissue; the expression level of TBC1D3 and its family proteins in renal clear cell carcinoma is closely related to the prognosis of the patient. The TBC1D3 provided by the invention can be used as a molecular marker for diagnosis and prognosis judgment of renal clear cell carcinoma and a target of a therapeutic drug. TBC1D3 family members can be targeted for immunotherapy of renal clear cell carcinoma.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of TBC1D3 and families thereof in preparation of tumor diagnosis medicines and prognosis judgment medicines.
Background
Clear cell carcinoma of the kidney is the most common malignancy in kidney cancers, accounting for 75-82% of primary renal malignancies. Renal clear cell carcinoma has been demonstrated to be a highly immunoinvasive tumor, one of the earliest immunotherapeutic tumors, in various clinical and genomic studies. Since renal clear cell carcinoma is not susceptible to conventional radiotherapy and chemotherapy, its treatment relies mainly on targeted therapy and immunotherapy. Targeted therapies include tyrosine kinase inhibitors such as sunitinib and sorafenib. However, tumor heterogeneity, dynamics, and alterations in the adaptive cell death-related signaling pathways to therapy significantly limit the use of targeted drugs in renal clear cell carcinoma therapy.
Disclosure of Invention
According to the invention, the expression of TBC1D3 and the family gene thereof in renal clear cell carcinoma tissues is found to be remarkably higher than that of paracarcinoma normal tissues through an online database; the expression level of TBC1D3 and its family protein in renal clear cell carcinoma is closely related to the prognosis of patients, and the overall survival rate of patients with high expression level of TBC1D3 and its family protein in renal clear cell carcinoma tissue is lower than that of patients with low expression. Meanwhile, the TBC1D3 plasmid is constructed, and the transfected renal clear cell carcinoma cells are found to promote cell proliferation. TBC1D3 family members were also found to be associated with immunoinfiltration.
RNA interference (RNAi) refers to the specific degradation of intracellular mRNA mediated by endogenous or exogenous double-stranded RNA, resulting in silencing of the expression of the target gene, resulting in the loss of the corresponding functional phenotype. It can block the expression of specific gene in body efficiently and specially to result in its degradation, so that it can cause the silencing of specific gene in the body and make the cell show the deletion of some gene phenotype. Currently, RNAi-specific gene expression inhibitors have been used in gene therapy for genetic diseases, viral infectious diseases, and cancer.
Use of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3D, TBC1D3E, TBC1D3F, TBC1D3G or TBC1D3H as a tumor diagnostic and prognostic marker.
In one embodiment of the present invention, the nucleotide sequences of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3D, TBC1D3E, TBC1D3F, TBC1D3G or TBC1D3H are shown in SEQ ID No.1 to SEQ ID No.8, respectively.
In one embodiment of the invention, the tumor is renal clear cell carcinoma, renal papillary cell carcinoma, liver cancer, lung adenocarcinoma, lung squamous cell carcinoma, and thyroid cancer.
The RNA interference target sequences of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3D, TBC1D3E, TBC1D3F, TBC1D3G or TBC1D3H are respectively shown in SEQ ID NO.9-SEQ ID NO. 14.
The RNA interference target sequence of the TBC1D3, the TBC1D3B, the TBC1D3C, the TBC1D3F, the TBC1D3G or the TBC1D3H is applied to the preparation of a tumor treatment drug.
In one embodiment of the invention, the tumor is renal clear cell carcinoma, renal papillary cell carcinoma, liver cancer, lung adenocarcinoma, lung squamous cell carcinoma or thyroid carcinoma.
An antitumor drug, which contains the RNA interference target sequence of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3F, TBC1D3G or TBC1D 3H.
In one embodiment of the invention, the medicament further comprises an inhibitor that inhibits CD4+ T cells or T cell depletion.
In one embodiment of the invention, the tumor is renal clear cell carcinoma, renal papillary cell carcinoma, liver cancer, lung adenocarcinoma, lung squamous cell carcinoma or thyroid carcinoma.
In one embodiment of the present invention, the RNA interference target sequences of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3F, TBC1D3G or TBC1D3H are shown as SEQ ID No.9-SEQ ID No.14, respectively.
Compared with the prior art, the technical scheme of the invention has the following advantages:
the invention firstly proves that the TBC1D3 and the family thereof are kidney clear cell carcinoma prognosis markers, and firstly discovers that the TBC1D3 can be used as molecular markers for diagnosis and prognosis judgment of kidney clear cell carcinoma and targets of therapeutic drugs. TBC1D3 family members can be targeted for immunotherapy of renal clear cell carcinoma.
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In order that the present disclosure may be more readily and clearly understood, reference will now be made in detail to the present disclosure, examples of which are illustrated in the accompanying drawings
FIGS. 1-1 and 1-2 are the analysis of the expression of TBC1D3 pan-carcinoma according to the present invention, the expression of TBC1D3 family in TCGA database.
FIG. 2 is a genomic alteration of a TBC1D3 family member and a gene-gene and protein-protein interaction network of a TBC1D3 family gene in accordance with the present invention.
FIGS. 3-1, 3-2 and 3-3 show the prognostic expression of a member of the TBC1D3 family in renal clear cell carcinoma in accordance with the present invention.
FIG. 4 is a graph of the function of a TBC1D3 family member in renal clear cell carcinoma in accordance with the present invention.
FIGS. 5-1, 5-2, 5-3 and 5-4 show the correlation between the TBC1D3 family protein and the immunosuppressant in the present invention.
FIG. 6-1, FIG. 6-2, FIG. 6-3, FIG. 6-4 and FIG. 6-5 show the correlation between the TBC1D3 family member protein and the immunoinfiltration of renal clear cell carcinoma in accordance with the present invention.
FIGS. 7-1, 7-2, and 7-3 are graphs showing the correlation between the level of immunoinfiltration of renal clear cell carcinoma in accordance with the present invention and the change in the copy number of different somatic cells of a member of the TBC1D3 family.
Detailed Description
The present invention is further described below in conjunction with the following figures and specific examples so that those skilled in the art may better understand the present invention and practice it, but the examples are not intended to limit the present invention.
Example 1 expression of TBC1D3 and its family in renal clear cell carcinoma
TBC1D3 expression in renal clear cell carcinoma by GSCA database analysis. TBC1D3 expression was found to be highly expressed in renal clear cell carcinoma, renal papillary cell carcinoma, liver cancer, lung adenocarcinoma, lung squamous cell carcinoma and thyroid carcinoma, and low expressed in head and neck squamous cell carcinoma. We found that TBC1D3 family (TBC1D3, TBC1D3B, TBC1D3C, TBC1D3D, TBC1D3E, TBC1D3F, TBC1D3G, TBC1D3H) are highly expressed in renal clear cell carcinoma compared to paracancer tissues by analyzing the data through the R language, both through the UALCAN database and downloading the TCGA data.
Example 2 genetic alterations of genes and protein networks of TBC1D3 and its families
We used the cbbioport database to determine the type and frequency of TBC1D3 family changes in TCGA KIRC samples. The results show that TBC1D3 family members are rarely mutated (less than 5 frequencies), which is highly conserved (see figure 2-a for results). Then, we analyzed five members of TBC1D3 family using "correlation analysis" by cbiportal, and the results showed that there was a positive correlation between TBC1D3 family members, but a negative correlation between TBC1D3C and TBC1D3G (see fig. 2-D for results). The gene-gene and protein-protein interaction networks generated using GeneMANIA and STRING showed that 20 potential target genes and 11 potential target proteins interacted with TBC1D3 family (see results in fig. 2-B and fig. 2-C).
Example 3 prognostic expression of TBC1D3 family members in renal clear cell carcinoma
The effect of TBC1D3 family expression on survival was evaluated using GSCA, TISIDB, LinkedOmics and Kaplan-Meier plotters. GSCA analysis showed that TBC1D3 expression in KIRC-multiple tumors was positively correlated with OS and PFS. In addition, highly expressed TBC1D3 survived for a short time (see results in FIG. 3-1). Total survival analysis of TISIDB and LinkedOmics showed that patients with high expression of TBC1D3 family members had a shorter overall survival time (results are shown in FIGS. 3-2 and 3-3). To further investigate the role of TBC1D3 in KIRC clinical characteristics, we investigated the relationship between TBC1D3 expression and KIRC clinical pathological characteristics using a Kaplan-Meier mapper. As shown in table 1, high expression of TBC1D3 and TBC1D3B was associated with OS exacerbation in stage I, II, III, IV, grade 3 and grade 4 patients. To investigate whether TBC1D3 expression is an independent predictor of KIRC patient overall survival, we performed univariate and multivariate Cox regression analyses. Single factor Cox regression analysis showed that age, grade, stage, TNM grade were independent risk factors for OS (p ═ 0.012, 3.61E-08, 1.26E-10, 2.69E-08, 2.76E-10, and 0.001); in multivariate Cox regression analysis, age, grade and TBC1D3 expression were independent risk factors for OS (p ═ 0.0003, 0.014 and 0.013, respectively) (results are shown in table 2).
TABLE 1
Note: bold letters indicate p < 0.05.
TABLE 2
Note: bold letters indicate p < 0.05.
TABLE 3
Note: TAM, tumor-associated macrophages; th, T helper cells; tfh, follicular helper T cells; tregs, regulatory T cells; p < 0.01; p < 0.001; p < 0.0001.
Example 4 function of TBC1D3 in renal clear cell carcinoma
To investigate the function of the TBC1D3 family in KIRC, we performed single cell analysis using cancer sea. The results indicate that TBC1D3D positively regulates proliferation of KIRC cells, negatively regulating inflammation (fig. 4A-B). We constructed TBC1D3 plasmid and transfected Caki-1 cells, and showed that TBC1D3 promoted proliferation of renal clear cell carcinoma cells (see FIG. 4-C). The biological processes of TBC1D3 were identified by overexpression enrichment analysis (ORA), and the results indicated that TBC1D3 expression correlates well with immune responses (see fig. 4-D).
Example 5 correlation of TBC1D3 family expression with immunosuppressants in renal clear cell carcinoma
The TISIDB database was selected to study the relationship between TBC1D3 family expression and immunosuppressive effects. Thus, TBC1D3, TBC1D3B, TBC1D3C and TBC1D3G are four members of the TBC1D3 family, associated with CD160, CTLA4, CD244, KDR, LAG3, PDCD1, PDCD1LG2 and TIGIT, respectively. In addition, TGFBR1 and HAVCR2 are related to TBC1D3, TBC1D3B and TBC1D 3G. CD274 is associated with TBC1D3B, TBC1D3C, and TBC1D 3G. In addition, TBC1D3 is associated with LGALS 9. TBC1D3B is related to CD 274. TBC1D3C is related to CD96 and LGALS 9. TBC1D3G correlated with IL10RB and PVRL2 (see results in FIGS. 5-1, 5-2, 5-3, 5-4).
Example 6 correlation of TBC1D3 family expression with immune infiltration in renal clear cell carcinoma
The TIMER database was used to investigate the relationship between TBC1D3 family expression and renal clear cell carcinoma infiltrating lymphocytes. TBC1D3 family expression was positively correlated with CD4+ T cell infiltration levels. Furthermore, macrophage infiltration levels were only significantly correlated with TBC1D3 expression, and dendritic cell infiltration levels were negatively correlated with TBC1D3B expression. The neutrophil infiltration level was positively correlated with TBC1D3 and TBC1D3H expression (see fig. 6-1, fig. 6-2, fig. 6-3, fig. 6-4, fig. 6-5). To further confirm the relationship between TBC1D3 expression in KIRC and immune cell infiltration levels, we used the TIMER database to explore the relationship between TBC1D3 expression and various immune infiltration-related markers. Our results show that there is a significant correlation between TBC1D3 expression and most of the markers of neutrophil, Th1, Th2, Treg and T cell failure (results see table 3). In particular, T cells were depleted, consistent with DISTIB analysis. The Somatic Copy Number Alteration (SCNA) module showed that arm level loss of TBC1D3 family members correlated significantly with the level of immune cell infiltration in renal clear cell carcinoma (results see fig. 7-1, fig. 7-2, fig. 7-3).
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art based on the foregoing description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications of the invention may be made without departing from the spirit or scope of the invention.
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agacugggag aaauacaaaa gcagcagaaa gcucauagau cgagcguaca agggaaugcc 420
caugaacauc cggggcccga uguggucagu ccuccugaac acugaggaaa ugaaguugaa 480
aaaccccgga agauaccaga ucaugaagga gaagggcaag aggucaucug agcacaucca 540
gcgcaucgac cgggacguaa gcgggacauu aaggaagcau auauucuuca gggaucgaua 600
cggaaccaag cagcgggaac uacuccacau ccuccuggca uaugaggagu acaacccgga 660
ggugggcuac ugcagggacc ugagccacau cgccgccuug uuccuccucu aucuuccuga 720
ggaggaugca uucugggcac uggugcagcu gcuggccagu gagaggcacu cccugcaggg 780
auuucacagc ccaaauggcg ggaccgucca ggggcuccaa gaccaacagg agcauguggu 840
agccacguca caacccaaga ccauggggca ucaggacaag aaagaucuau gugggcagug 900
uuccccguua ggcugccuca uccggauauu gauugacggg aucucucucg ggcucacccu 960
gcgccugugg gacguguauc ugguagaagg cgaacaggcg uugaugccga uaacaagaau 1020
cgccuuuaag guucagcaga agcgccucac gaagacgucc agguguggcc cgugggcacg 1080
uuuuugcaac cgguucguug auaccugggc cagggaugag gacacugugc ucaagcaucu 1140
uagggccucu augaagaaac uaacaagaaa gaagggggac cugccacccc cagccaaacc 1200
cgagcaaggg ucgucggcau ccaggccugu gccggcuuca cguggcggga agacccucug 1260
caagggggac aggcaggccc cuccaggccc accagcccgg uucccgcggc ccauuugguc 1320
agcuuccccg ccacgggcac cucguucuuc cacacccugu ccuggugggg cuguccggga 1380
agacaccuac ccugugggca cucagggugu gcccagcccg gcccuggcuc agggaggacc 1440
ucaggguucc uggagauucc ugcaguggaa cuccaugccc cgccucccaa cggaccugga 1500
cguagagggc ccuugguucc gccauuauga uuucaggcag agcugcuggg uccgugccau 1560
aucccaggag gaccagcugg cccccugcug gcaggcugaa cacccugcgg agcgggugag 1620
aucggcuuuc gcugcaccca gcacugauuc cgaccagggc acccccuuca gagcuaggga 1680
cgaacagcag ugugcuccca ccucagggcc uugccucugc ggccuccacu uggaaaguuc 1740
ucaguucccu ccaggcuucu agaagcaucu gggccagggc ucauggcugg auaauuuccc 1800
uaggcuuaac aacccaagca agcuucgcau ccucguuuua uuuuugguua aacuuaugaa 1860
aauguauuaa gaaagagugc agcucgagag agauucagag auggaacaca ccagacccca 1920
gaucacaaag ccaaccaugc ccagccccuc ccagcacccc cagccccacg accaucguuc 1980
ugaauucuga cgacaccgug agccugccuu uguacuucaa acucauggaa ggauaaccac 2040
cuucauguuu ugaaauaaau guuuccuguu gaaauga 2077
<210> 2
<211> 1620
<212> RNA
<213> (Artificial Synthesis)
<400> 2
agaaugucac uggugcuuag caccuaucug cucucuggcc ugccucagug gucuacagca 60
guuacacaca ggcaguggua ucugugagca gcucugugga cucaaagguu uucucccuga 120
gaggcaugac ccaggccagc ugauucauca gaaucaggau ggacguggua gaggucgcgg 180
guaguuggug ggcacaagag cgagaggaca ucauuaugaa auacgaaaag ggacaccgag 240
cugggcugcc agaggacaag gggccuaagc cuuuucgaag cuacaacaac aacgucgauc 300
auuuggggau uguacaugag acggagcugc cuccucugac ugcgcgggag gcgaagcaaa 360
uucggcggga gaucagccga aagagcaagu ggguggauau gcugggagac ugggagaaau 420
acaaaagcag cagaaagcuc auagaucgag cguacaaggg aaugcccaug aacauccggg 480
gcccgaugug gucaguccuc cugaacauug aggaaaugaa guugaaaaac cccggaagau 540
accagaucau gaaggagaag ggcaagaggu caucugagca cauccagcgc aucgaccggg 600
acauaagcgg gacauuaagg aagcauaugu ucuucaggga ucgauacgga accaagcagc 660
gggaacuacu ccacauccuc cuggcauaug aggaguauaa cccggaggug ggcuacugca 720
gggaccugag ccacaucgcc gccuuguucc uccucuaucu uccugaggag gaugcauucu 780
gggcacuggu gcagcugcug gccagugaga ggcacucccu gcagggauuu cacagcccaa 840
auggcgggac cguccagggg cuccaagacc aacaggagca ugugguagcc acgucacaau 900
ccaagaccau ggggcaucag gacaagaaag aucuaugugg gcaguguucc ccguuaggcu 960
gccucauccg gauauugauu gacgggaucu cucucgggcu cacccugcgc cugugggacg 1020
uguaucuggu agaaggcgaa caggcguuga ugccgauaac aagaaucgcc uuuaagguuc 1080
agcagaagcg ccucacgaag acguccaggu guggcccgug ggcacguuuu ugcaaccggu 1140
ucguugauac cugggccagg gaugaggaca cugugcucaa gcaucuuagg gccucuauga 1200
agaaacuaac aagaaagcag ggggaccugc cacccccagc caaacccgag caagggucgu 1260
cggcauccag gccugugccg gcuucacgug gcaggaagac ccucugcaag ggggacaggc 1320
aggccccucc aggcccacca gcccgguucc cgcggcccau uuggucagcu uccccgccac 1380
gggcaccucg uucuuccaca cccuguccug guggggcugu ccgggaagac accuacccug 1440
ugggcacuca gggugugccc agcccggccc uggcucaggg aggaccucag gguuccugga 1500
gauuccugca guggaacucc augccccgcc ucccaacgga ccuggacgua gaggggccuu 1560
gguuccgcca uuaugauuuc agacagagcu gcuggguccg ugccauaucc caggaggacc 1620
<210> 3
<211> 1620
<212> RNA
<213> (Artificial Synthesis)
<400> 3
agcaccuauc ugcucucugg ucugccucag uggucuacag caguuacaca caggcagugg 60
uaucugugag cagcucugug gacucaaagg uuuucucccu gagaggcacg acccaggcca 120
gcugauucau cagaaucagg auggacgugg uagaggucgc gggcaguugg ugggcacaag 180
agcgagagga caucauuaug aaauacgaaa agggacaccg agcugggcug ccagaggaca 240
aggggccuaa gccuuuucga agcuacaaca acaacgucga ucauuugggg auuguacaug 300
agacggagcu gccuccucug acugcgcggg aggcgaagca aauucggcgg gagaucagcc 360
gaaagagcaa guggguggau augcugggag acugggagaa auacaaaagc agcagaaagc 420
ucauagaucg agcguacaag ggaaugccca ugaacauccg gggcccgaug uggucagucc 480
uccugaacac ugaggaaaug aaguugaaaa accccggaag auaccagauc augaaggaga 540
agggcaagag gucaucugag cacauccagc gcaucgaccg ggacguaagc gggacauuaa 600
ggaagcauau auucuucagg gaucgauacg gaaccaagca gcgggaacua cuccacaucc 660
uccuggcaua ugaggaguac aacccggagg ugggcuacug cagggaccug agccacaucg 720
ccgccuuguu ccuccucuau cuuccugagg aggaugcauu cugggcacug gugcagcugc 780
uggccaguga gaggcacucc cugcagggau uucacagccc aaauggcggg accguccagg 840
ggcuccaaga ccaacaggag caugugguag ccacgucaca acccaagacc auggggcauc 900
aggacaagaa agaucuaugu gggcaguguu ccccguuagg cugccucauc cggauauuga 960
uugacgggau cucucucggg cucacccugc gccuguggga cguguaucug guagaaggcg 1020
aacaggcguu gaugccgaua acaagaaucg ccuuuaaggu ucagcagaag cgccucacga 1080
agacguccag guguggcccg ugggcacguu uuugcaaccg guucguugau accugggcca 1140
gggaugagga cacugugcuc aagcaucuua gggccucuau gaagaaacua acaagaaaga 1200
agggggaccu gccaccccca gccaaacccg agcaaggguc gucggcaucc aggccugugc 1260
cggcuucacg uggcgggaag acccucugca agggggacag gcaggccccu ccaggcccac 1320
cagcccgguu cccgcggccc auuuggucag cuuccccgcc acgggcaccu cguucuucca 1380
cacccugucc ugguggggcu guccgggaag acaccuaccc ugugggcacu cagggugugc 1440
ccagcccggc ccuggcucag ggaggaccuc aggguuccug gagauuccug caguggaacu 1500
ccaugccccg ccucccaacg gaccuggacg uagagggccc uugguuccgc cauuaugauu 1560
ucagacagag cugcuggguc cgugccauau cccaggagga ccagcuggcc cccugcuggc 1620
<210> 4
<211> 2065
<212> RNA
<213> (Artificial Synthesis)
<400> 4
caguuacaca caggcagugg uaucugugag cagcucugug gacucaaagg uuuucucccu 60
gagaggcacg acccaggcca gcugauucau cagaaucagg auggacgugg uagaggucgc 120
gggcaguugg ugggcacaag agcgagagga caucauuaug aaauacgaaa agggacaccg 180
agcugggcug ccagaggaca aggggccuaa gccuuuucga agcuacaaca acaacgucga 240
ucauuugggg auuguacaug agacggagcu gccuccucug acugcgcggg aggcgaagca 300
aauucggcgg gagaucagcc gaaagagcaa guggguggau augcugggag acugggagaa 360
auacaaaagc agcagaaagc ucauagaucg agcguacaag ggaaugccca ugaacauccg 420
gggcccgaug uggucagucc uccugaacac ugaggaaaug aaguugaaaa accccggaag 480
auaccagauc augaaggaga agggcaagag gucaucugag cacauccagc gcaucgaccg 540
ggacguaagc gggacauuaa ggaagcauau auucuucagg gaucgauacg gaaccaagca 600
gcgggaacua cuccacaucc uccuggcaua ugaggaguau aacccggagg ugggcuacug 660
cagggaccug agccacaucg ccgccuuguu ccuccucuau cuuccugagg aggaugcauu 720
cugggcacug gugcagcugc uggccaguga gaggcacucc cugcagggau uucacagccc 780
aaauggcggg accguccagg ggcuccaaga ccaacaggag caugugguag ccacgucaca 840
acccaagacc auggggcauc aggacaagaa agaucuaugu gggcaguguu ccccguuagg 900
cugccucauc cggauauuga uugacgggau cucucucggg cucacccugc gccuguggga 960
cguguaucug guagaaggcg aacaggcguu gaugccgaua acaagaaucg ccuuuaaggu 1020
ucagcagaag cgccucacga agacguccag guguggcccg ugggcacguu uuugcaaccg 1080
guucguugau accugggcca gggaugagga cacugugcuc aagcaucuua gggccucuau 1140
gaagaaacua acaagaaagc agggggaccu gccaccccca gccaaacccg agcaaggguc 1200
gucggcaucc aggccugugc cggcuucacg uggcgggaag acccucugca agggggacag 1260
gcaggccccu ccaggcccac cagcccgguu cccgcggccc auuuggucag cuuccccgcc 1320
acgggcaccu cguucuucca cacccugucc ugguggggcu guccgggaag acaccuaccc 1380
ugugggcacu cagggugugc ccagcccggc ccuggcucag ggaggaccuc aggguuccug 1440
gagauuccug caguggaacu ccaugccccg ccucccaacg gaccuggacg uagagggccc 1500
uugguuccgc cauuaugauu ucagacagag cugcuggguc cgugccauau cccaggagga 1560
ccagcuggcc cccugcuggc aggcugaaca cccugcggag cgggugagau cggcuuucgc 1620
ugcacccagc acugauuccg accagggcac ccccuucaga gcuagggacg aacagcagug 1680
ugcucccacc ucagggccuu gccucugcgg ccuccacuug gaaaguucuc aguucccucc 1740
aggcuucuag aagcaucugg gccagggcuc auggcuggau aauuucccua ggcuuaacaa 1800
cccaagcaag cuucgcaucc ucguuuuauu uuugguuaaa cuuaugaaaa uguauuaaga 1860
aagagugcag cucgagagag auucagagau ggaacacacc agaccccaga ucacaaagcc 1920
aaccaugccc ggccccuccc agcaccccca gccccacgac caucguucug aauucugacg 1980
acaccgugag ccugccuuug uacuucaaac ucauggaagg auaaccaccu ucauguuuug 2040
aaauaaaugu uuccuguuga aauga 2065
<210> 5
<211> 2082
<212> RNA
<213> (Artificial Synthesis)
<400> 5
gccucagugg ucuacagcag uuacacacag gcagugguau cugugagcag cucuguggac 60
ucaaagguuu ucucccugag aggcaugacc caggccagcu gauucaucag aaucaggaug 120
gacgugguag aggucgcggg caguuggugg gcacaagagc gagaggacau cauuaugaaa 180
uacgaaaagg gacaccgagc ugggcugcca gaggacaagg ggccuaagcc uuuucgaagc 240
uacaacaaca acgucgauca uuuggggauu guacaugaga cggagcugcc uccucugacu 300
gcgcgggagg cgaagcaaau ucggcgggag aucagccgaa agagcaagug gguggauaug 360
cugggagacu gggagaaaua caaaagcagc agaaagcuca uagaucaagc guacaaggga 420
augcccauga acauccgggg cccgaugugg ucaguccucc ugaacacuga ggaaaugaag 480
uugaaaaacc ccggaagaua ccagaucaug aaggagaagg gcaagaaguc aucugagcac 540
auccagcgca ucgaccggga cguaagcggg acauuaagga agcauauauu cuucagggau 600
cgauacggaa ccaagcagcg ggaacuacuc cacauccucc uggcauauga ggaguacaac 660
ccggaggugg gcuacugcag ggaccugagc cacaucgccg ccuuguuccu ccucuaucuu 720
ccugaggagg augcauucug ggcacuggug cagcugcugg ccagugagag gcacucccug 780
cagggauuuc acagcccaaa uggcgggacc guccaggggc uccaagacca acaggagcau 840
gugguagcca cgucacaacc caagaccaug gggcaucagg acaagaaaga ucuauguggg 900
caguguuccc cguuaggcug ccucauccgg auauugauug acgggaucuc ucucgggcuc 960
acccugcgcc ugugggacgu guaucuggua gaaggcgaac aggcgcugau gccgauaaca 1020
agaaucgccu uuaagguuca gcagaagcgc cucacgaaga cguccaggug uggcccgugg 1080
gcacguuuuu gcaaccgguu cguugauacc ugggccaggg augaggacac ugugcucaag 1140
caucuuaggg ccucuaugaa gaaacuaaca agaaagaagg gggaccugcc acccccagcc 1200
aaacccgagc aagggucguc ggcauccagg ccugugccgg cuucacgugg cgggaagacc 1260
cucugcaagg gggacaggca ggccccucca ggcccaccag cccgguuccc gcggcccauu 1320
uggucagcuu ccccgccacg ggcaccucgu ucuuccacac ccuguccugg uggggcuguc 1380
cgggaagaca ccuacccugu gggcacucag ggugugccca gcccggcccu ggcucaggga 1440
ggaccucagg guuccuggag auuccugcag uggaacucca ugccccgccu cccaacggac 1500
cuggacguag agggcccuug guuccgccau uaugauuuca gacagagcug cuggguccgu 1560
gccauauccc aggaggacca gcuggccccc ugcuggcagg cugaacaccc ugcggagcgg 1620
gugagaucgg cuuucgcugc acccagcacu gauuccgacc agggcacccc cuucagagcu 1680
agggacgaac agcagugugc ucccaccuca gggccuugcc ucugcggccu ccacuuggaa 1740
aguucucagu ucccuccagg cuucuagaag caucugggcc agggcucaug gcuggauaau 1800
uucccuaggc uuaacaaccc aagcaagcuu cgcauccucg uuuuauuuuu gguuaaacuu 1860
augaaaaugu auuaagaaag agugcagcuc gagagagauu cagagaugga acacaccaga 1920
ccccagauca caaagccaac caugcccagc cccucccagc acccccagcc ccacgaccau 1980
cguucugaau ucugacgaca ccgugagccu gccuuuguac uucaaacuca uggaaggaua 2040
accaccuuca uguuuugaaa uaaauguuuc cuguugaaau ga 2082
<210> 6
<211> 2077
<212> RNA
<213> (Artificial Synthesis)
<400> 6
aguggucuac agcaguuaca cacaggcagu gguaucugug agcagcucug uggacucaaa 60
gguuuucucc cugagaggca ugacccaggc cagcugauuc aucagaauca ggauggacgu 120
gguagagguc gcggguaguu ggugggcaca agagcgagag gacaucauua ugaaauacga 180
aaagggacac cgagcugggc ugccagagga caaggggccu aagccuuuuc gaagcuacaa 240
caacaacguc gaucauuugg ggauuguaca ugagacggag cugccuccuc ugacugcgcg 300
ggaggcgaag caaauucggc gggagaucag ccgaaagagc aagugggugg auaugcuggg 360
agacugggag aaauacaaaa gcagcagaaa gcucauagau cgagcguaca agggaaugcc 420
caugaacauc cggggcccga uguggucagu ccuccugaac auugaggaaa ugaaguugaa 480
aaaccccgga agauaccaga ucaugaagga gaagggcaag aggucaucug agcacaucca 540
gcgcaucgac cgggacguaa gcgggacauu aaggaagcau auauucuuca gggaucgaua 600
cggaaccaag cagcgggaac uacuccacau ccuccuggca uaugaggagu acaacccgga 660
ggugggcuac ugcagggacc ugagccacau cgccgccuug uuccuccucu aucuuccuga 720
ggaggaugca uucugggcac uggugcagcu gcuggccagu gagaggcacu cccugcaggg 780
auuucacagc ccaaauggcg ggaccgucca ggggcuccaa gaccaacagg agcauguggu 840
agccacguca caacccaaga ccauggggca ucaggacaag aaagaucuau gugggcagug 900
uuccccguua ggcugccuca uccggauauu gauugacggg aucucucucg ggcucacccu 960
gcgccugugg gacguguauc ugguagaagg cgaacaggcg uugaugccga uaacaagaau 1020
cgccuuuaag guucagcaga agcgccucac gaagacgucc agguguggcc cgugggcacg 1080
uuuuugcaac cgguucguug auaccugggc cagggaugag gacacugugc ucaagcaucu 1140
uagggccucu augaagaaac uaacaagaaa gaagggggac gugccacccc cagccaaacc 1200
cgagcaaggg ucgucggcau ccaggccugu gccggcuuca cguggcggga agacccucug 1260
caagggggac agacaggccc cuccaggccc accagcccgg uucccgcggc ccauuugguc 1320
agcuuccccg ccacgggcac cucguucuuc cacacccugu ccuggugggg cuguccggga 1380
agacaccuac ccugugggca cucagggugu gcccagcccg gcccuggcuc agggaggacc 1440
ucaggguucc uggagauucc ugcaguggaa cuccaugccc cgccucccaa ccgaccugga 1500
cguagagggc ccuugguucc gccauuauga uuucagacag agcugcuggg uccgugccau 1560
aucccaggag gaccagcugg cccccugcug gcaggcugaa cacccugcgg agcgggugag 1620
aucggcuuuc gcugcaccca gcacugauuc cgaccagggc acccccuuca gagcuaggga 1680
cgaacagcag ugugcuccca ccucagggcc uugccucugc ggccuccacu uggaaaguuc 1740
ucaguucccu ccaggcuucu agaagcaucu gggccagggc ucauggcugg auaauuuccc 1800
uaggcuuaac aacccaagca agcuucgcau ccucguuuua uuuuugguua aacuuaugaa 1860
aauguauuaa gaaagagugc agcucgagag agauucagag auggaacaca ccagacccca 1920
gaucacaaag ccaaccaugc ccagccccuc ccagcacccc cagccccacg accaucguuc 1980
ugaauucuga cgacaccgug agccugccuu uguacuucaa acucauggaa ggauaaccac 2040
cuucauguuu ugaaauaaau guuuccuguu gaaauga 2077
<210> 7
<211> 2065
<212> RNA
<213> (Artificial Synthesis)
<400> 7
caguuacaca caggcagugg uaucugugag cagcucugug gacucaaagg uuuucucccu 60
gagaggcaug acccaggcca gcugauucau cagaaucagg auggacgugg uagaggucgc 120
gggcaguugg ugggcacaag agcgagagga caucauuaug aaauacgaaa agggacaccg 180
agcugggcug ccagaggaca aggggccuaa gccuuuucga agcuacaaca acaacgucga 240
ucauuugggg auuguacaug agacggagcu gccuccucug acugcgcggg aggcgaagca 300
aauucggcgg gagaucagcc gaaagagcaa guggguggau augcugggag acugggagaa 360
auacaaaagc agcagaaagc ucauagaucg agcguacaag ggaaugccca ugaacauccg 420
gggcccgaug uggucagucc uccugaacau ugaggaaaug aaguugaaaa accccggaag 480
auaccagauc augaaggaga agggcaagag gucaucugag cacauccagc gcaucgaccg 540
ggacauaagc gggacauuaa ggaagcauau guucuucagg gaucgauacg gaaccaagca 600
gcgggaacua cuccacaucc uccuggcaua ugaggaguau aacccggagg ugggcuacug 660
cagggaccug agccacaucg ccgccuuguu ccuccucuau cuuccugagg aggaugcauu 720
cugggcacug gugcagcugc uggccaguga gaggcacucc cugcagggau uucacagccc 780
aaauggcggg accguccagg ggcuccaaga ccaacaggag caugugguag ccacgucaca 840
acccaagacc auggggcauc aggacaagaa agaucuaugu gggcaguguu ccccguuagg 900
cugccucauc cggauauuga uugacgggau cucucucggg cucacccugc gccuguggga 960
cguguaucug guagaaggcg aacaggcguu gaugccgaua acaagaaucg ccuuuaaggu 1020
ucagcagaag cgccucacga agacguccag guguggcccg ugggcacguu uuugcaaccg 1080
guucguugau accugggcca gggaugagga cacugugcuc aagcaucuua gggccucuau 1140
gaagaaacua acaagaaagc agggggaccu gccaccccca gccaaacccg agcaaggguc 1200
gucggcaucc aggccugugc cggcuucacg uggcgggaag acccucugca agggggacag 1260
gcaggccccu ccaggcccac cagcccgguu cccgcggccc auuuggucag cuuccccgcc 1320
acgggcaccu cguucuucca cacccugucc ugguggggcu guccgggaag acaccuaccc 1380
ugugggcacu cagggugugc ccagcccggc ccuggcucag ggaggaccuc aggguuccug 1440
gagauuccug caguggaacu ccaugccccg ccucccaacg gaccuggacg uagagggccc 1500
uugguuccgc cauuaugauu ucagacagag cugcuggguc cgugccauau cccaggagga 1560
ccagcuggcc cccugcuggc aggcugaaca cccugcggag cgggugagau cggcuuucgc 1620
ugcacccagc acugauuccg accagggcac ccccuucaga gcuagggacg aacagcagug 1680
ugcucccacc ucagggccuu gccucugcgg ccuccacuug gaaaguucuc aguucccucc 1740
aggcuucuag aagcaucugg gccagggcuc auggcuggau aauuucccua ggcuuaacaa 1800
cccaagcaag cuucgcaucc ucguuuuauu uuugguuaaa cuuaugaaaa uguauuaaga 1860
aagagugcag cucgagagag auucagagau ggaacacacc agaccccaga ucacaaagcc 1920
aaccaugccc agccccuccc agcaccccca gccccacgac caucguucug aauucugacg 1980
acaccgugag ccugccuuug uacuucaaac ucauggaagg auaaccaccu ucauguuuug 2040
aaauaaaugu uuccuguuga aauga 2065
<210> 8
<211> 2077
<212> RNA
<213> (Artificial Synthesis)
<400> 8
aguggucuac agcaguuaca cacaggcagu gguaucugug agcagcucug uggacucaaa 60
gguuuucucc cugagaggca ugacccaggc cagcugauuc aucagaauca ggauggacgu 120
gguagagguc gcgggcaguu ggugggcaca agagcgagag gacaucauua ugaaauacga 180
aaagggacac cgagcugggc ugccagagga caaggggccu aagccuuuuc gaagcuacaa 240
caacaacguc gaucauuugg ggauuguaca ugagacggag cugccuccuc ugacugcgcg 300
ggaggcgaag caaauucggc gggagaucag ccgaaagagc aagugggugg auaugcuggg 360
agacugggag aaauacaaaa gcagcagaaa gcucauagau cgagcguaca agggaaugcc 420
caugaacauc cggggcccga uguggucagu ccuccugaac acugaggaaa ugaaguugaa 480
aaaccccgga agauaccaga ucaugaagga gaagggcaag aggucaucug agcacaucca 540
gcgcaucgac cgggacauaa gcgggacauu aaggaagcau auguucuuca gggaucgaua 600
cggaaccaag cagcgggaac uacuccacau ccuccuggca uaugaggagu auaacccgga 660
ggugggcuac ugcagggacc ugagccacau cgccgccuug uuccuccucu aucuuccuga 720
ggaggaugca uucugggcac uggugcagcu gcuggccagu gagaggcacu cccugcaggg 780
auuucacagc ccaaauggcg ggaccgucca ggggcuccaa gaccaacagg agcauguggu 840
agccacguca caacccaaga ccauggggca ucaggacaag aaagaucuau gugggcagug 900
uuccccguua ggcugccuca uccggauauu gauugacggg aucucucucg ggcucacccu 960
gcgccugugg gacguguauc ugguagaagg cgaacaggcg uugaugccga uaacaagaau 1020
cgccuuuaag guucagcaga agcgccucac gaagacgucc agguguggcc cgugggcacg 1080
uuuuugcaac cgguucguug auaccugggc cagggaugag gacacugugc ucaagcaucu 1140
uagggccucu augaagaaac uaacaagaaa gcagggggac cugccacccc cagccaaacc 1200
cgagcaaggg ucgucggcau ccaggccugu gccggcuuca cguggcggga agacccucug 1260
caagggggac aggcaggccc cuccaggccc accagcccgg uucccgcggc ccauuugguc 1320
agcuuccccg ccacgggcac cucguucuuc cacacccugu ccuggugggg cuguccggga 1380
agacaccuac ccugugggca cucagggugu gcccagcccg gcccuggcuc agggaggacc 1440
ucaggguucc uggagauucc ugcaguggaa cuccaugccc cgccucccaa cggaccugga 1500
cguagagggc ccuugguucc gccauuauga uuucagacag agcugcuggg uccgugccau 1560
aucccaggag gaccagcugg cccccugcug gcaggcugaa cacccugcgg agcgggugag 1620
aucggcuuuc gcugcaccca gcacugauuc cgaccagggc acccccuuca gagcuaggga 1680
cgaacagcag ugugcuccca ccucagggcc uugccucugc ggccuccacu uggaaaguuc 1740
ucaguucccu ccaggcuucu agaagcaucu gggccagggc ucauggcugg auaauuuccc 1800
uaggcuuaac aacccaagca agcuucgcau ccucguuuua uuuuugguua aacuuaugaa 1860
aauguauuaa gaaagagugc agcucgagag agauucagag auggaacaca ccagacccca 1920
gaucacaaag ccaaccaugc ccagccccuc ccagcacccc cagccccacg accaucguuc 1980
ugaauucuga cgacaccgug agccugccuu uguacuucaa acucauggaa ggauaaccac 2040
cuucauguuu ugaaauaaau guuuccuguu gaaauga 2077
<210> 9
<211> 21
<212> RNA
<213> (Artificial Synthesis)
<400> 9
uaggcugccu cauccggaua u 21
<210> 10
<211> 21
<212> RNA
<213> (Artificial Synthesis)
<400> 10
gcuugagaga cauucagaga u 21
<210> 11
<211> 21
<212> RNA
<213> (Artificial Synthesis)
<400> 11
cgauaacaag aaucgccuuu a 21
<210> 12
<211> 21
<212> RNA
<213> (Artificial Synthesis)
<400> 12
ccagaucaca aagccaacca u 21
<210> 13
<211> 21
<212> RNA
<213> (Artificial Synthesis)
<400> 13
auaacaagaa ucgccuuuaa g 21
<210> 14
<211> 21
<212> RNA
<213> (Artificial Synthesis)
<400> 14
aggcguugau gccgauaaca a 21
Claims (9)
- Use of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3D, TBC1D3E, TBC1D3F, TBC1D3G or TBC1D3H as a tumor diagnostic and prognostic marker.
- 2. The use as claimed in claim 1, wherein the nucleotide sequences of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3D, TBC1D3E, TBC1D3F, TBC1D3G and TBC1D3H are shown as SEQ ID No.1-SEQ ID No.8, respectively.
- 3. The use of claim 1, wherein the tumor is renal clear cell carcinoma, renal papillary cell carcinoma, liver cancer, lung adenocarcinoma, lung squamous cell carcinoma, or thyroid cancer.
- The RNA interference target sequences of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3F, TBC1D3G and TBC1D3H are shown in SEQ ID NO.9-SEQ ID NO.14, respectively.
- 5. Use of the RNA interference target sequence of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3F, TBC1D3G or TBC1D3H of claim 4 in the preparation of a medicament for the treatment of tumors.
- 6. The use of claim 5, wherein the tumor is renal clear cell carcinoma, renal papillary cell carcinoma, liver cancer, lung adenocarcinoma, lung squamous cell carcinoma, or thyroid cancer.
- 7. An anti-tumor drug comprising the RNA interference target sequence of TBC1D3, TBC1D3B, TBC1D3C, TBC1D3F, TBC1D3G or TBC1D3H according to claim 4.
- 8. The medicament of claim 7, further comprising CD4+ T cells or an inhibitor of T cell depletion.
- 9. The medicament of claim 7, wherein the tumor is renal clear cell carcinoma, renal papillary cell carcinoma, liver cancer, lung adenocarcinoma, lung squamous cell carcinoma or thyroid carcinoma.
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Citations (2)
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| US20030044814A1 (en) * | 2001-02-08 | 2003-03-06 | Tularik Inc. | PRC17: an amplified cancer gene |
| CN102203291A (en) * | 2008-08-28 | 2011-09-28 | 肿瘤疗法科学股份有限公司 | Tbc1d7 as tumor marker and therapeutic target for cancer |
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2021
- 2021-06-23 CN CN202110699497.0A patent/CN113584163A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030044814A1 (en) * | 2001-02-08 | 2003-03-06 | Tularik Inc. | PRC17: an amplified cancer gene |
| CN102203291A (en) * | 2008-08-28 | 2011-09-28 | 肿瘤疗法科学股份有限公司 | Tbc1d7 as tumor marker and therapeutic target for cancer |
Non-Patent Citations (3)
| Title |
|---|
| BEI WANG等: "TBC1D3 family is a prognostic biomarker and correlates with immune infiltration in kidney renal clear cell carcinoma", 《MOLECULAR THERAPY: ONCOLYTICS》 * |
| DORIT ARLT等: "Functional Profiling: From Microarrays via Cell-Based Assays to Novel Tumor Relevant Modulators of the Cell Cycle", 《CANCER RESEARCH》 * |
| 王北: "癌基因TBC1D3诱导人乳腺癌细胞迁移的机制", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
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Application publication date: 20211102 |