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Gene information | Literature | Expression | lncRNA | Mutation | Homolog

Basic Information

Gene ID

100126333

Name

MIR708

Synonymous

microRNA 708;MIR708;microRNA 708

Definition

-

Position

11q14.1

Gene type

ncRNA

Title

Abstract

Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from never smokers.

PURPOSE: miRNA plays an important role in human disease and cancer. We seek to investigate the expression status, clinical relevance, and functional role of miRNA in non-small cell lung cancer. EXPERIMENTAL DESIGN: We conducted miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 56 pairs of fresh-frozen (FF) and 47 pairs of formalin-fixed, paraffin-embedded (FFPE) samples from never smokers. The most differentially expressed miRNA genes were evaluated by Cox analysis and log-rank test. Among the best candidate, miR-708 was further examined for differential expression in two independent cohorts. Functional significance of miR-708 expression in lung cancer was examined by identifying its candidate mRNA target and through manipulating its expression levels in cultured cells. RESULTS: Among the 20 miRNAs most differentially expressed between tested tumor and normal samples, high expression level of miR-708 in the tumors was most strongly associated with an increased risk of death after adjustments for ALL clinically significant factors including age, sex, and tumor stage (FF cohort: HR, 1.90; 95% CI, 1.08-3.35; P = 0.025 and FFPE cohort: HR, 1.93; 95% CI, 1.02-3.63; P = 0.042). The transcript for TMEM88 gene has a miR-708 binding site in its 3 UTR and was significantly reduced in tumors high of miR-708. Forced miR-708 expression reduced TMEM88 transcript levels and increased the rate of cell proliferation, invasion, and migration in culture. CONCLUSIONS: miRNA-708 acts as an oncogene contributing to tumor growth and disease progression by directly downregulating TMEM88, a negative regulator of the Wnt signaling pathway in lung cancer.

miR-708 promotes the development of bladder carcinoma via direct repression of Caspase-2.

PURPOSE: Bladder cancer is one of the world s top ten malignant tumors. The crucial role of microRNA in carcinogenesis has been well emphasized. Considering miRNA expression was tumor stage-, tissue-, or even development-specific, more experimental evidences about the functions of miRNAs in bladder cancer should be discovered to advance applying of miRNA in the diagnosis or therapy of cancer. METHODS: MiR-708 level in bladder carcinoma and adjacent noncancerous tissues was tested by real-time qPCR. Cell apoptosis was analyzed by using flow cytometry. The tumorigenicity of bladder carcinoma cells was evaluated in nude mice model. Luciferase reporter gene assays were performed to identify the interaction between miR-708 and 3 UTR of Caspase-2 mRNA. The protein level of Caspase-2 was determined by western blotting. RESULTS: In this study, we reported that miR-708 was frequently dysregulated in human bladder carcinoma tissues compared to normal tissues. In addition, we found that silencing of miR-708 could promote the T24 and 5637 cells to apoptosis and inhibit the bladder tumor growth in vivo. Also, Caspase-2 was proved to be one of direct targets of miR-708 in T24 and 5637 cells. Further results showed that Caspase-2 was involved in the miR-708 regulated cell apoptosis. CONCLUSIONS: ALL together, these results suggest miR-708 may act as an oncogene and induce the carcinogenicity of bladder cancer by down-regulating Caspase-2 level.