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CircRNA ZNF609 Knockdown Represses the Development of Non-Small Cell Lung Cancer via miR-623/FOXM1 Axis

Fanghan Wang1, Xiangfeng Li2, Xigao Jia3

  • 1Department of Oncology, 4th People's Hospital of Zibo, Zibo, Shandong, 255000, People's Republic of China.

Cancer Management and Research
|February 12, 2021
PubMed
Abstract

Insights

Circular RNA zinc finger protein 609 (circZNF609) promotes non-small cell lung cancer (NSCLC) progression. Knockdown of circZNF609 inhibits NSCLC development by regulating microRNA-623 and forkhead box M1.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are implicated in non-small cell lung cancer (NSCLC) pathogenesis.
  • The specific role of circRNA zinc finger protein 609 (circZNF609) in NSCLC remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the function and molecular mechanism of circZNF609 in the development of NSCLC.
  • To investigate the regulatory pathway involving circZNF609, microRNA-623 (miR-623), and forkhead box M1 (FOXM1) in NSCLC.

Main Methods:

  • Quantitative reverse transcription polymerase chain reaction and Western blot were used to measure circZNF609, miR-623, and FOXM1 levels in 62 NSCLC patients.
  • Cellular assays (CCK8, flow cytometry, caspase3 activity, transwell) assessed the impact of circZNF609 on NSCLC cell viability, apoptosis, migration, and invasion.
  • Dual-luciferase reporter assays, RNA immunoprecipitation, and pull-down assays identified interactions between circZNF609, miR-623, and FOXM1. In vivo studies utilized a xenograft model.

Main Results:

  • circZNF609 expression was significantly upregulated in NSCLC tissues and cells, correlating with lower overall survival.
  • circZNF609 knockdown suppressed NSCLC cell viability, migration, and invasion while promoting apoptosis.
  • circZNF609 was found to target miR-623, which in turn targets FOXM1. circZNF609 regulates FOXM1 expression. Knockdown of circZNF609 inhibited tumor growth in vivo.

Conclusions:

  • circZNF609 knockdown effectively represses NSCLC progression.
  • The mechanism involves the circZNF609/miR-623/FOXM1 axis, highlighting its potential as a therapeutic target.
Keywords:
FOXM1circZNF609miR-623non-small cell lung cancer

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