miR-138-5p contributes to cell proliferation and invasion by targeting Survivin in bladder cancer cells

Abstract

BackgroundSurvivin (encoded by the gene BIRC5) plays an important role in the carcinogenesis of bladder cancer. Identifying miRNAs that target Survivin in the setting of bladder cancer will help to develop Survivin-based therapies for bladder cancer.MethodsThe expression levels of miR-138-5p and Survivin protein were measured in 12 resected bladder cancer specimens. The correlation between miR-138-5p and Survivin was further examined by evaluating Survivin expression in human bladder cancer cell lines that either overexpressed or knocked down miR-138-5p. A luciferase reporter assay was performed to test the direct binding of miR-138-5p to the target gene BIRC5. We also investigated the biological role of miR-138-5p targeting to Survivin in bladder cancer cell lines both in vivo and in vitro.ResultsIn this study, we found that the Survivin protein was either absent or weakly expressed in normal adjacent tissues and consistently up-regulated in bladder cancer tissues; however, the mRNA levels did not vary as much, suggesting that a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for microRNAs that could potentially target BIRC5 in the setting of bladder cancer. We identified 2 specific targeting sites for miR-138-5p in the 3′ untranslated region (3′-UTR) of BIRC5. We further identified an inverse correlation between miR-138-5p and Survivin protein levels in bladder cancer tissue samples. By overexpressing or knocking down miR-138-5p in bladder cancer cells, we experimentally confirmed that miR-138-5p directly recognizes the 3′-UTR of the BIRC5 transcript and regulates Survivin expression. Furthermore, the biological consequences of the targeting of BIRC5 by miR-138-5p were examined in vitro via cell proliferation and invasion assays and in vivo using a mouse xenograft tumor model. We demonstrated that BIRC5 repression by miR-138-5p suppressed the proliferative and invasive characteristics of bladder cancer cells and that miR-138-5p exerted an anti-tumor effect by negatively regulating BIRC5 in a xenograft mouse model.ConclusionsTaken together, our findings provide the first clues regarding the role of miR-138-5p as a tumor suppressor in bladder cancer by inhibiting BIRC5 translation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-016-0569-4) contains supplementary material, which is available to authorized users.

LncRNA FENDRR represses proliferation, migration and invasion through suppression of survivin in cholangiocarcinoma cells

“…On the other hand, survivin is an oncogene that regulates the apoptosis, proliferation, and invasion of many cancers [25][26][27]. Knockdown of survivin by using siRNA could dramatically suppress the proliferation and invasion of bladder cancer cells [8]. Co-silencing of Livin and Survivin can effectively inhibit the cell proliferation and apoptosis of lung cancer cells [28].…”

“…Survivin expression is minimal in normal tissues; therefore, it has become a lead target for both as a tumor diagnostic, prognostic and for anti-cancer therapies. Mounting evidence has demonstrated that survivin takes part in the regulation of cell cycle, apoptosis, cell proliferation as well as invasion and play important roles in various tumor carcinogenesis, such as gastric cancer [7], bladder cancer [8], epithelial ovarian cancer [9].…”

miRNA‑26a‑5p and miR‑26b‑5p inhibit the proliferation of bladder cancer cells by regulating PDCD10

“…Several researchers have reported that there are many miRNAs that play a part in regulating the progression of cancer. Yang et al (19) reported that miR-138-5p is a tumor suppressor that inhibits cell proliferation and invasion by targeting Survivin. In prostate cancer, papillary thyroid carcinoma, and head and neck carcinoma, both miR-26a-5p and miR-26b-5p could inhibit tumor progression (20)(21)(22).…”

Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus

“…Interestingly, the downregulation of miR-138-5p plays an important role in various cancers. For example, it was reported that miR-138-5p could inhibit BIRC5 translation and suppress the BIRC5-meditated carcinogenesis of bladder cancer [45]. Similarly, miR-138-5p was also downregulated in human colorectal cancer (CRC) and dramatically promoted CRC cell growth and tumorigenesis by targeting PD-L1 [46].…”