MiR-133b regulates bladder cancer cell proliferation and apoptosis by targeting Bcl-w and Akt1

Abstract

BackgroundMiR-133b is a muscle-specific microRNA; it has a role in the formation of cardiocytes and the expression of myocardium ion channels by regulating target genes. Many human malignant tumors demonstrate a low expression of miR-133b, as noted in colorectal, lung, esophagus and bladder cancers, but the role of miR-133b in bladder cancer is unknown.MethodsThe expression of miR-133b in clinical bladder cancer specimens and adjacent normal tissues was confirmed by stem-loop RT-PCR. We also analyzed the relationship between miR-133b expression and clinicopathological factors of bladder cancer. Bcl-w and Akt1 protein expression in 41 bladder cancer specimens and adjacent normal tissues was detected by Western blot. After transfection of miR-133b mimics or inhibitor into a T24 human bladder cancer cell line, Bcl-w and Akt1 protein and mRNA expression were examined by Western blot and RT-PCR, respectively. The effect of miR-133b on T24 cell proliferation and apoptosis was measured by CCK-8 tests and flow cytometry, respectively.ResultsThe expression of miR-133b in bladder cancer tissues from 41 patients was significantly down-regulated (P < 0.01); low expression of miR-133b was strongly associated with high-grade bladder cancer (P < 0.01). Bcl-w and Akt1 proteins were significantly overexpressed in bladder cancer tissues versus adjacent normal tissues (P < 0.01 for both). The expression of Akt1 and Bcl-w proteins and Akt1 mRNA, in T24 cells was significantly down-regulated or up-regulated after transfection of miR-133b mimics or inhibitor, respectively; however, there was no significant difference in Bcl-w mRNA expression. Transfection of HEK-293 T cells with miR-133b significantly suppressed a luciferase-reporter containing the Bcl-w or Akt 1 3′-untranslated regions. MiR-133b mimics significantly inhibited T24 cell proliferation, as well as increased T24 cell apoptosis (P < 0.05 and P < 0.01, respectively) while the miR-133b inhibitor increased and decreased these, respectively (P < 0.05 for both).ConclusionsMiR-133b may play a very important role in the proliferation and apoptosis of T24 cells by regulating the expression of Bcl-w and Akt1.

MicroRNA-133b inhibits the migration and invasion of non small cell lung cancer cells via targeting FSCN1

“…The regulatory mechanism of miR-133b in the regulation of human cancers including NSCLC has been widely studied (9,19,20). Crawford et al suggested that two members of the B cell lymphoma-2 (BCL-2) family, myeloid cell leukemia 1 (MCL-1) and BCL-2 like 2, were targets of miR-133b, and that the overexpression of miR-133b induced apoptosis following exposure to gemcitabine in lung adenocarcinoma H2009 cells (18).…”

Downregulation of miR‐133b predict progression and poor prognosis in patients with urothelial carcinoma of bladder

“…The mechanism for altered miR‐133b expression associating with prognosis of oncological patients had been revealed by many functional studies of miR‐133b. Our previous study demonstrated that miR‐133b could regulate proliferation and apoptosis of bladder cancer cells by targeting Bcl‐w and Akt1 13. Consistently, Zhou et al.…”

“…12 suggested that renal cell carcinoma patients with higher miR‐194 expression has significantly longer disease‐free survival and overall survival compared to those with lower expression. Our previous studies had shown that miR‐133b could inhibit the proliferation of bladder cancer cells and induce apoptosis in bladder cancer cells, which indicated that miR‐133b play an important role in tumorigenesis and progression of UCB 13. We want to validate the importance of miR‐133b in UCB by analyzing the relationship between the expression of miR‐133b and clinicopathological characteristics of UCB.…”

Overexpression of microRNA-133b sensitizes non-small cell lung cancer cells to irradiation through the inhibition of glycolysis

“…As it has been previously reported that miR-133b acts as a tumor suppressor in lung cancer, the expression levels of miR-133b in A549 cells were measured following radiation treatment (13)(14)(15)(16)(17)(18). The expression of miR-133b was significantly reduced following radiation treatments of 0.2 to 0.6 Gy (Fig.…”

“…Recently, the role of miRNA-21 within NSCLC radioresistance has been identified, indicating that miRNAs may be selected as a possible therapeutic target (12). Additionally, miR-133b in particular has been reported to function as a tumor suppressor in multiple types of cancer (13)(14)(15). However, the precise role of miR-133b within radiosensitivity is not yet clear.…”