LncRNA XIST promotes bladder cancer progression by modulating miR-129-5p/TNFSF10 axis.

BACKGROUND: The differential expression, biological function, and ceRNA regulatory mechanism of lncRNA XIST in bladder cancer (BC) were investigated, and its clinical values for the early diagnosis of bladder cancer patients were elucidated. METHODS: qRT-PCR was employed to detect the expression patterns of lncRNA XIST, miR-129-5p and TNFSF10. The biological functions were measured by CCK8 assay, wound healing assay and transwell assay. Bioinformatics analysis and Dual-Luciferase reporter assay were employed to evaluate the interactions between the lncRNA XIST, miR-129-5p and TNFSF10. RESULTS: LncRNA XIST and TNFSF10 were highly expressed and miR-129-5p was low expressed (P < 0.05) in bladder cancer cell line. The depletion of lncRNA XIST inhibited BC proliferation, migration and invasion. Mechanistically, lncRNA XIST could sponge miR-129-5p to regulate TNFSF10 expression in bladder cancer. Furthermore, compared with adjacent tissues, lncRNA XIST and miR-129-5p were lowly expressed (P < 0.01) in bladder cancer tissues, and TNFSF10 was highly expressed (P < 0.001). miR-129-5p and TNFSF10 were associated with the risk of bladder cancer (P < 0.05); the difference in AUC values for the diagnosis of bladder cancer by lncRNA XIST (AUC = 0.739), miR-129-5p (AUC = 0.850) and TNFSF10 (AUC = 0.753) was statistically significant (P < 0.01), and the three genes combined AUC was 0.900, 95%CI was 0.842-0.958 with a sensitivity of 83.3% and specificity of 86.7%. CONCLUSION: XIST, an elevated lncRNA in bladder cancer, inhibition of which could suppress the progression of BC. LncRNA XIST and miR-129-5p could form ceRNA to regulate the expression of TNFSF10.

Methylation of the suppressor of cytokine signaling 3 gene (SOCS3) in bladder cancer.

BACKGROUND: It has been identified consequences of dysregulation of JAK-STAT signalling, particularly in regard to JAK-STAT signalling that has been shown to have roles in the oncogenesis of several cell types. SOCS3 protein, the negative regulatory protein of JAK-STAT signaling pathway, may also plays critical regulatory roles in cancer initiation and progression. SOCS3 promoter hypermethylation has often been identified in human cancers; however, the precise role of SOCS3 in bladder cancer is unclear. METHODS: The methylation status of the SOCS3 was analyzed in an age (±5 years) and sex-matched case-control study, including 112 bladder cancer cases and 118 normal controls, using the MassARRAY EpiTYPER system. RESULTS: Methylation rate of JAK2, SOCS3 and STAT3 gene were shown to vary among different CpG island. The methylation rate of SOCS3 gene was also much higher in BCa than in normal control participants, but the methylation rate of JAK2, STAT3 gene weren't different in Bca and normal control participants. CONCLUSIONS: Our study demonstrates that promoter hypermethylation of SOCS3 gene is associated with BCa and thus, may serve as an independent prognostic biomarker.