MiR-138 induces renal carcinoma cell senescence by targeting EZH2 and is downregulated in human clear cell renal cell carcinoma

Jiaqian Liang, Yajing Zhang, Guosong Jiang, Zhouqiang Liu, Wei Xiang, Xuanyu Chen, Zhaohui Chen, Jun Zhao

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

MiR-138 has been shown to be downregulated in various cancers, including head and neck squamous cell carcinoma (HNSCC) and clear cell renal carcinoma (ccRCC). In the present study, we aimed to reveal the mechanism of miR-138 induction of senescence in renal carcinoma cells and identify its specific target genes. We used qRT-PCR to analyze miR-138 expression levels in renal carcinoma cell lines and ccRCC samples. The activity of β-galactOsidase was measured for functional analysis after miR-138 mimic transfeclion. To identify the targets of miR-138, we used three types of target prediction software to determine three candidate target genes. Furthermore, a 3'UTR luciferase assay was performed. Western blotting was used to detect the protein expression levels of candidate target genes. Additionally, knockdown of EZH2 by its siRNA was performed. The expression of miR-138 was downregulated in RCC cells lines and in tumor samples compared with their controls. Transfeclion of miR-138 mimic induced SN-12 cell senescence, decreased the protein expression of EZH2, and increased the protein expression of P16. Furthermore, miR-138 decreased the 3'UTR luciferase activity of EZH2. The knockdown of EZH2 by siRNA induced SN-12 cell senescence, decreased the protein expression level of EZH2, and increased the protein expression of P16. MiR-138 is a tumor-suppressor miRNA in ccRCC that induces SN-12 cell senescence by downrcgulating EZH2 expression and upregulaling P16 expression.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalOncology Research
Volume21
Issue number2
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • EZH2
  • MiR-138
  • Pi6
  • Renal carcinoma
  • Senescence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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