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Circ TYMP1 Inhibits Carcinogenesis and Cisplatin Resistance in Ovarian Cancer by Reducing Smad2/3 Phosphorylation via

Yang Rao1, Wenwen Zhang2, Dan Li3

  • 1Department of Gynecological Oncology, Tianjin Central Hospital of Gynecology and Obstetrics, Tianjin 300100, China.

Contrast Media & Molecular Imaging
|September 8, 2022
PubMed

Insights

Circular TYMP1 (circ TYMP1) drives ovarian carcinoma progression and cisplatin resistance by sponging miR-182A-3p, which increases TGF1B. Reducing circ TYMP1 inhibits cancer growth and chemoresistance, offering new therapeutic avenues.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Thymidine phosphorylase 1 (TYMP1) is implicated in various cancers, but its role in ovarian carcinoma is unclear.
  • Ovarian carcinoma is a significant global health concern, often developing resistance to chemotherapy like cisplatin (DDP).

Purpose of the Study:

  • To elucidate the function of circ TYMP1 in ovarian carcinoma development and cisplatin resistance.
  • To investigate the molecular mechanisms underlying circ TYMP1's action in ovarian cancer.

Main Methods:

  • Bioinformatic analysis to identify circ TYMP1 targets.
  • In vitro experiments using ovarian carcinoma cell lines (A2780-Res) to assess the effects of circ TYMP1 and miR-182A-3p manipulation.
  • Assessment of cell proliferation, invasion, apoptosis resistance, and TGF1B signaling pathways.

Main Results:

  • Overexpression of circ TYMP1 correlated with advanced tumor stage in ovarian carcinoma patients.
  • Circ TYMP1 acts as a molecular sponge for miR-182A-3p, inhibiting its tumor-suppressive function.
  • Downregulation of circ TYMP1 reduced ovarian cancer cell proliferation, invasion, and cisplatin resistance.
  • Restoring miR-182A-3p function reversed the pro-cancerous effects induced by circ TYMP1.
  • TGF1B overexpression promoted ovarian cancer cell proliferation, aggression, and cisplatin resistance.

Conclusions:

  • Circ TYMP1 promotes ovarian carcinoma carcinogenesis and cisplatin resistance by sequestering miR-182A-3p and consequently upregulating TGF1B.
  • Targeting the circ TYMP1/miR-182A-3p/TGF1B axis presents a potential therapeutic strategy for ovarian cancer.

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