Dataset Information

MiR-193a-5p Targets the Coding Region of AP-2? mRNA and Induces Cisplatin Resistance in Bladder Cancers.

ABSTRACT: Transcription factor AP-2 alpha (AP-2? or TFAP2A) is a newly identified prognostic marker of chemotherapy; its expression is positively correlated with chemosensitivity and survival of cancer patients. Using computational programs, we predicted that the coding region of AP-2? gene contains a potential miRNA response element (MRE) of miR-193a-5p, and the single nucleotide polymorphism (SNP) site (c.497A>G, rs111681798) resides within the predicted MRE. The results of luciferase assays and Western blot analysis demonstrated that miR-193a-5p negatively regulated the expression of AP-2? proteins, but have no influence on the mutant AP-2? (c.497A>G). Infection with lentiviral AP-2? gene or miR-193a-5p inhibitor in the bladder cancer cells decreased migration and cisplatin resistance, while knockdown of AP-2? gene or overexpression of miR-193a-5p in the urothelial cell line SV-HUC-1 increased migration and cisplatin resistances. We concluded that miR-193a-5p induced cisplatin resistance by repressing AP-2? expression in bladder cancer cells.

SUBMITTER: Zhou J

PROVIDER: S-EPMC5039396 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers.

Zhou Ji J Duan Huaxin H Xie Yu Y Ning Yichong Y Zhang Xing X Hui Na N Wang Chunqing C Zhang Jian J Zhou Jianlin J

Journal of Cancer 20160807 12

Transcription factor AP-2 alpha (AP-2α or TFAP2A) is a newly identified prognostic marker of chemotherapy; its expression is positively correlated with chemosensitivity and survival of cancer patients. Using computational programs, we predicted that the coding region of AP-2α gene contains a potential miRNA response element (MRE) of miR-193a-5p, and the single nucleotide polymorphism (SNP) site (c.497A>G, rs111681798) resides within the predicted MRE. The results of luciferase assays and Western ...[more]

PMID: 27698912

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Project description:Identifying genes with prognostic importance could improve cancer treatment. An increasing number of reports suggest the existence of successful strategies based on seemingly "untargetable" transcription factors. In addition to embryogenesis, AP-2 transcription factors are known to play crucial roles in cancer development. Members of this family can be used as prognostic factors in oncological patients, and AP-2α/γ transcription factors were previously investigated in our pan-cancer comparative study using their target genes. The present study investigates tumors that were previously found similar with an emphasis on the possible role of AP-2 factors in specific cancer types. The RData workspace was loaded back to R environment and 3D trajectories were built via Monocle3. The genes that met the requirement of specificity were listed using top_markers(), separately for mutual and unique targets. Furthermore, the candidate genes had to meet the following requirements: correlation with AP-2 factor (through Correlation AnalyzeR) and validated prognostic importance (using GEPIA2 and subsequently KM-plotter or LOGpc). Eventually, the ROC analysis was applied to confirm their predictive value; co-dependence of expression was visualized via BoxPlotR. Some similar tumors were differentiated by AP-2α/γ targets with prognostic value. Requirements were met by only fifteen genes (EMX2, COL7A1, GRIA1, KRT1, KRT14, SLC12A5, SEZ6L, PTPRN, SCG5, DPP6, NTSR1, ARX, COL4A3, PPEF1 and TMEM59L); of these, the last four were excluded based on ROC curves. All the above genes were confronted with the literature, with an emphasis on the possible role played by AP-2 factors in specific cancers. Following ROC analysis, the genes were verified using immunohistochemistry data and progression-related signatures. Staining differences were observed, as well as co-dependence on the expression of e.g. CTNNB1, ERBB2, KRAS, SMAD4, EGFR or MKI67. In conclusion, prognostic value of targets suggested AP-2α/γ as candidates for novel cancer treatment. It was also revealed that AP-2 targets are related to tumor progression and that some mutual target genes could be inversely regulated.

Dataset Information

MiR-193a-5p Targets the Coding Region of AP-2? mRNA and Induces Cisplatin Resistance in Bladder Cancers.

Publications

MiR-193a-5p Targets the Coding Region of AP-2α mRNA and Induces Cisplatin Resistance in Bladder Cancers.

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