A circular RNA, circSMARCA5, inhibits prostate cancer proliferative, migrative, and invasive capabilities via the

Xin Xie1, Fu-Kang Sun1, Xin Huang1

  • 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

Aging
|August 14, 2021
PubMed

Insights

Circular RNA SMARCA5 (circSMARCA5) is downregulated in prostate cancer, suppressing metastasis and growth. It regulates TIMP3 expression via miR-181b-5p/miR-17-3p, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The role of SMARCA5 (circSMARCA5) in prostate cancer progression and metastasis is not well understood.
  • circSMARCA5 is implicated in various cancers, but its specific function in prostate cancer remains elusive.

Purpose of the Study:

  • To investigate the functional significance of circSMARCA5 in prostate cancer.
  • To elucidate the molecular mechanisms underlying circSMARCA5's role in prostate cancer carcinogenesis and metastasis.

Main Methods:

  • Quantitative real-time PCR and Western blot assays were used to assess circSMARCA5 and TIMP3 expression.
  • RNA immunoprecipitation, biotin-coupled microRNA capture, and luciferase reporter assays were employed to determine molecular interactions.
  • Prostate cancer tissues and cell lines were utilized for functional and mechanistic studies.

Main Results:

  • circSMARCA5 expression was significantly downregulated in primary and metastatic prostate cancer tissues compared to normal controls.
  • circSMARCA5 demonstrated a suppressive effect on prostate cancer cell growth and metastasis.
  • circSMARCA5 regulates Tissue Inhibitor of Metalloproteinases 3 (TIMP3) expression through interactions with miR-181b-5p and miR-17-3p.
  • Lysine acetyltransferase 5 (KAT5) was found to induce circSMARCA5 biogenesis and modulate the miR-181b-5p-TIMP3/miR-17-3p-TIMP3 axis.

Conclusions:

  • circSMARCA5 acts as a tumor suppressor in prostate cancer by inhibiting metastasis and growth.
  • The circSMARCA5-miR-181b-5p-TIMP3 and circSMARCA5-miR-17-3p-TIMP3 axes represent novel molecular pathways in prostate cancer.
  • Targeting these circSMARCA5-mediated pathways could offer a new therapeutic strategy for prostate cancer treatment.

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