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

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• 作者：Xiao Peng Mao (1)
  Luo Sheng Zhang (2)
  Bin Huang (1)
  Shi Ying Zhou (1)
  Jun Liao (1)
  Ling Wu Chen (2)
  Shao Peng Qiu (1)
  Jun Xing Chen (1)
  
  1. Department of Urology ; the First Affiliated Hospital ; Sun Yat-Sen University ; Guangzhou ; 510080 ; PR China
  2. Oncology Department ; PLA458 Hospital ; Guangzhou ; 510000 ; China
  
• 关键词：Bladder cancer ; miR ; 135a ; PHLPP2 ; FOXO1 ; Proliferation
• 刊名：Journal of Translational Medicine
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：13
• 期：1
• 全文大小：1,889 KB
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• 刊物主题：Biomedicine general; Medicine/Public Health, general;
• 出版者：BioMed Central
• ISSN：1479-5876

文摘

Background Bladder 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. Methods The 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. Results miR-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. Conclusion Our study demonstrates that miR-135a promotes cell proliferation in bladder cancer by targeting PHLPP2 and FOXO1, and is performed as an onco-miR.