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Inhibition of miR-221 influences bladder cancer cell proliferation and apoptosis

H Liu1, J-K Chang, J-Q Hou

  • 1Department of Urology, Huaihe Hospital, Henan University, Kaifeng, China. xiangbokonggt@163.com.

European Review for Medical and Pharmacological Sciences
|August 4, 2017
PubMed
Abstract

Insights

MicroRNA-221 (miR-221) promotes bladder cancer by suppressing SOCS3, which activates the JAK-STAT3 pathway. Inhibiting miR-221 reduces cancer cell proliferation and increases apoptosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway regulates cell proliferation and apoptosis.
  • Suppressors of cytokine signaling 3 (SOCS3) act as negative regulators of the JAK-STAT3 pathway.
  • SOCS3 expression is decreased, while microRNA-221 (miR-221) is increased in bladder cancer tissues.

Purpose of the Study:

  • To investigate the role of miR-221 in regulating the SOCS3/JAK-STAT3 signaling pathway.
  • To determine the effect of miR-221 on bladder cancer cell proliferation and apoptosis.

Main Methods:

  • Analysis of miR-221 and SOCS3 expression in bladder cancer and adjacent tissues.
  • Dual luciferase assay to confirm the targeting of SOCS3 by miR-221.
  • In vitro studies using T24 bladder cancer cells and HBEC cells to assess the impact of miR-221 inhibition and SOCS3 restoration on cell proliferation, apoptosis, and signaling pathway activation.

Main Results:

  • Bladder cancer tissues exhibited significantly higher miR-221 and lower SOCS3 levels compared to para-carcinoma tissues.
  • miR-221 directly targets and inhibits SOCS3 expression.
  • In T24 cells, miR-221 up-regulation correlated with increased p-JAK1, p-JAK2, p-STAT3, and survivin, and decreased SOCS3.
  • Inhibition of miR-221 or restoration of SOCS3 expression reversed these effects, enhancing apoptosis and reducing proliferation.

Conclusions:

  • miR-221 is upregulated and SOCS3 is downregulated in bladder cancer.
  • Inhibiting miR-221 suppresses bladder cancer cell proliferation and induces apoptosis.
  • These effects are mediated by restoring SOCS3 expression, reducing JAK-STAT3 pathway activity, and decreasing survivin levels.

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