Knockdown of circFGFR2 inhibits prostate cancer cell metastasis and proliferation by targeting miR-221-5p/ SMUG1

Wei Li1, Jiqing Fan1, Ling Deng1

  • 1Department of Urology, Shenzhen Longhua District Central Hospital, The Affiliated Longhua Hospital of Shenzhen University, Shenzhen, 518110, China.

Abstract

Insights

Circular RNA FGFR2 (circFGFR2) promotes prostate cancer (PC) progression by sponging miR-221-5p and upregulating SMUG1. Targeting circFGFR2 offers a potential therapeutic strategy for PC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer (PC) remains a significant health concern with a need for novel therapeutic targets.
  • Circular RNAs (circRNAs) have emerged as key regulators in various cancers, including PC.
  • Understanding the role of specific circRNAs like circFGFR2 is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the functional role of circFGFR2 in prostate cancer (PC) cells.
  • To identify the molecular mechanisms underlying circFGFR2's contribution to PC progression.
  • To explore circFGFR2 as a potential diagnostic biomarker and therapeutic target for PC.

Main Methods:

  • Quantitative reverse transcription PCR (qRTPCR) to assess circFGFR2 expression in PC tissues and cell lines.
  • In vitro assays (CCK-8, colony formation, Transwell, wound-healing) to evaluate the effects of circFGFR2 knockdown on PC cell behaviors.
  • Bioinformatics and luciferase reporter assays to determine interactions between circFGFR2, miR-221-5p, and SMUG1.
  • In vivo studies using a xenograft mouse model to assess circFGFR2's impact on tumor growth.

Main Results:

  • circFGFR2 was significantly upregulated in PC tissues and cell lines.
  • circFGFR2 knockdown inhibited PC cell invasion, migration, proliferation, and viability in vitro and tumor growth in vivo.
  • circFGFR2 acts as a competing endogenous RNA (ceRNA) by sponging miR-221-5p, leading to the downregulation of SMUG1.
  • Rescue experiments confirmed that circFGFR2 promotes PC progression via the miR-221-5p/SMUG1 pathway.

Conclusions:

  • circFGFR2 is a tumor-promoting circRNA in prostate cancer.
  • circFGFR2 functions by sponging miR-221-5p and consequently derepressing SMUG1 expression.
  • circFGFR2 represents a potential therapeutic target and a valuable biomarker for risk stratification and prognosis in PC.

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