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The putative tumour suppressor microRNA-145, repressed by c-jun, modulates clear cell renal cell carcinoma

Zhen Ding1, Xiao Zhang1, Zhu Qiao1

  • 1Department of Oncology, Affiliated Hospital of Jining Medical University Jining 272029, Shandong, China.

International Journal of Clinical and Experimental Pathology
|January 16, 2020
PubMed

Insights

MicroRNA-145 (miR-145) is downregulated in renal cell carcinoma (RCC), suppressing tumor growth and invasion. Restoring miR-145 may offer a new therapeutic strategy for clear cell RCC (ccRCC) patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Aberrant microRNA (miRNA) expression is implicated in various cancers.
  • The specific role of miR-145 in renal cell carcinoma (RCC) remains underexplored.
  • Renal cell carcinoma (RCC) is a significant global health concern.

Purpose of the Study:

  • To investigate the expression and function of miR-145 in clear cell renal cell carcinoma (ccRCC).
  • To identify the molecular mechanisms underlying miR-145 dysregulation in ccRCC.
  • To evaluate miR-145 as a potential therapeutic target for ccRCC.

Main Methods:

  • Quantitative real-time PCR to assess miR-145 expression in ccRCC tissues and cell lines.
  • Cell proliferation, invasion, and apoptosis assays to determine miR-145 function.
  • Luciferase reporter assays and Western blot to identify and validate miR-145 targets.
  • Immunohistochemistry to analyze the correlation between miR-145 and its target in patient tissues.
  • Epigenetic analysis to investigate the mechanism of miR-145 downregulation.

Main Results:

  • miR-145 was significantly downregulated in ccRCC tissues and cells, correlating with poor prognosis.
  • Restoration of miR-145 inhibited ccRCC cell proliferation and invasion while promoting apoptosis.
  • ROCK1 was identified as a direct target of miR-145, with inverse expression correlation in ccRCC tissues.
  • EZH2-mediated histone methylation was found to be responsible for miR-145 downregulation in ccRCC.

Conclusions:

  • miR-145 acts as a tumor suppressor in ccRCC progression.
  • miR-145 targets ROCK1, influencing ccRCC cell behavior.
  • EZH2-mediated epigenetic silencing contributes to miR-145 loss in ccRCC.
  • miR-145 holds promise as a potential therapeutic agent for ccRCC.
Keywords:
A498Clear cell renal cell carcinomaROCK1c-junmiR-145

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