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CircKEAP1 Suppresses the Progression of Lung Adenocarcinoma via the miR-141-3p/KEAP1/NRF2 Axis

Yanbo Wang1, Fenghai Ren1, Dawei Sun1

  • 1Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, Harbin, China.

Frontiers in Oncology
|June 17, 2021
PubMed
Abstract

Insights

Circular RNA circKEAP1 is downregulated in lung adenocarcinoma (LUAD), inhibiting tumor growth. It targets miR-141-3p, activating the KEAP1/NRF2 pathway to suppress LUAD progression, offering a potential new treatment strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lung adenocarcinoma (LUAD) is the most common and deadliest form of lung cancer.
  • Despite advances, LUAD pathogenesis remains incompletely understood.
  • This study investigates the role of circKEAP1, a circular RNA from the KEAP1 gene, in LUAD.

Purpose of the Study:

  • To identify the function of circKEAP1 in lung adenocarcinoma.
  • To elucidate the molecular mechanism by which circKEAP1 influences LUAD progression.
  • To explore circKEAP1 as a potential therapeutic target for LUAD.

Main Methods:

  • CircRNA expression profiling in LUAD tissues vs. adjacent non-tumor tissues using microarray.
  • Quantitative real-time PCR (qRT-PCR) to assess circKEAP1 levels and prognostic value.
  • In vitro and in vivo functional experiments to evaluate circKEAP1's effect on tumor growth.
  • Dual luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays to confirm molecular interactions.

Main Results:

  • circKEAP1 was significantly downregulated in LUAD tissues.
  • circKEAP1 suppressed tumor growth both in vitro and in vivo.
  • circKEAP1 competitively binds to miR-141-3p, relieving its repression on KEAP1.
  • This interaction activates the KEAP1/NRF2 signaling pathway, suppressing tumor progression.

Conclusions:

  • circKEAP1 inhibits LUAD progression via the circKEAP1/miR-141-3p/KEAP1 axis.
  • circKEAP1 acts as a tumor suppressor in LUAD.
  • circKEAP1 may represent a novel therapeutic target for lung adenocarcinoma treatment.
Keywords:
KEAP1cell proliferationcircKEAP1circRNAlung adenocarcinoma

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