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Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression

Gan Yu1, Weimin Yao1, Kiranmai Gumireddy2

  • 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Molecular Cancer Therapeutics
|September 25, 2014
PubMed

Insights

PTENP1, a pseudogene of the PTEN tumor suppressor gene, is downregulated in clear-cell renal cell carcinoma (ccRCC). Its restoration suppresses ccRCC progression and sensitizes cells to chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • PTENP1 is a pseudogene of the PTEN tumor suppressor gene (TSG).
  • The role of PTENP1 in clear-cell renal cell carcinoma (ccRCC) remains uncharacterized.
  • PTENP1 downregulation, via methylation, is observed in ccRCC tissues and cells.

Purpose of the Study:

  • To investigate the function of PTENP1 in ccRCC.
  • To elucidate the regulatory relationship between PTENP1, PTEN, and miR21 in ccRCC.
  • To assess the therapeutic potential of PTENP1 in ccRCC.

Main Methods:

  • Quantitative real-time PCR and methylation-specific PCR were used to assess PTENP1 expression and methylation status.
  • Western blotting and luciferase reporter assays were employed to confirm the targeting of PTENP1 and PTEN by miR21.
  • In vitro and in vivo assays were conducted to evaluate the effects of PTENP1 overexpression on ccRCC cell proliferation, migration, invasion, tumor growth, and metastasis.
  • Chemotherapy sensitivity assays were performed to assess the impact of PTENP1 on treatment response.

Main Results:

  • PTENP1 expression is significantly downregulated in ccRCC tissues and cells, correlated with increased methylation.
  • miR21 directly targets and suppresses both PTENP1 and PTEN expression in ccRCC.
  • Overexpression of PTENP1 inhibits ccRCC cell proliferation, migration, invasion, tumor growth, and metastasis, and sensitizes cells to cisplatin and gemcitabine.
  • Low PTENP1 expression in patients correlates with reduced survival rates.

Conclusions:

  • PTENP1 functions as a tumor suppressor in ccRCC.
  • PTENP1 acts as a competing endogenous RNA (ceRNA) by sponging miR21, thereby relieving the suppression of PTEN and other targets.
  • PTENP1 represents a potential therapeutic target for ccRCC treatment.

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