Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancerReport as inadecuate




Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer - Download this document for free, or read online. Document in PDF available to download.

Journal of Translational Medicine

, 13:86

First Online: 13 March 2015Received: 18 November 2014Accepted: 16 February 2015DOI: 10.1186-s12967-015-0438-8

Cite this article as: Mao, X.P., Zhang, L.S., Huang, B. et al. J Transl Med 2015 13: 86. doi:10.1186-s12967-015-0438-8

Abstract

BackgroundBladder cancer is the most common malignancy in urinary system and the ninth most common malignancy in the world. MicroRNAs miRNAs are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. We investigated the expression of miR-135a in bladder cancer and explored its bio-function during bladder cancer progression.

MethodsThe expression of miR-135a in bladder cancer cells and tissues are performed by using Real-time PCR assay. Cell viability assay MTT assay, colony formation assay, anchorage-independent growth ability assay and Bromodeoxyuridine labeling and immunofluorescence BrdUrd assay are used to examine cell proliferative capacity and tumorigenicity. Flow cytometry analysis is used to determine cell cycle progression. The expressions of p21, p27, CyclinD1, Ki67, PHLPP2 and FOXO1 are measured by Western blotting assay. Luciferase assay is used to confirm whether FOXO1 is the direct target of miR-135a.

ResultsmiR-135a is upregulated in bladder cancer cells and tissues. Enforced expression of miR-135a promotes bladder cancer cells proliferation, whereas inhibition of miR-135a reverses the function. Furthermore, for the first time we demonstrated PHLPP2 and FOXO1 are direct targets of miR-135a and transcriptionally down-regulated by miR-135a. Suppression of PHLPP2 or FOXO1 by miR-135a, consisted with dysregulation of p21, p27, Cyclin D1 and Ki67, play important roles in bladder cancer progression.

ConclusionOur study demonstrates that miR-135a promotes cell proliferation in bladder cancer by targeting PHLPP2 and FOXO1, and is performed as an onco-miR.

KeywordsBladder cancer miR-135a PHLPP2 FOXO1 Proliferation Xiao Peng Mao, Luo Sheng Zhang, Bin Huang and Shi Ying Zhou contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-015-0438-8 contains supplementary material, which is available to authorized users.

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Author: Xiao Peng Mao - Luo Sheng Zhang - Bin Huang - Shi Ying Zhou - Jun Liao - Ling Wu Chen - Shao Peng Qiu - Jun Xing Che

Source: https://link.springer.com/



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