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Hsa_circ_0005576 promotes osimertinib resistance through the miR-512-5p/IGF1R axis in lung adenocarcinoma cells

Suo Liu1, Zhibin Jiang1, Peng Xiao1

  • 1Department of Cardiothoracic Surgery, The Third Xiangya Hospital of Central South University, Changsha, China.

Cancer Science
|October 27, 2021
PubMed

Insights

Circular RNA hsa_circ_0005576 promotes osimertinib resistance in lung adenocarcinoma by sponging miR-512-5p and upregulating IGF1R. Knockdown enhances sensitivity, offering new therapeutic insights.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osimertinib, a third-generation EGFR-TKI, treats EGFR-mutant lung adenocarcinoma (LUAD).
  • Acquired resistance to osimertinib is a significant clinical challenge.
  • Circular RNAs (circRNAs) are implicated in drug resistance, but hsa_circ_0005576's role in LUAD osimertinib resistance is unexplored.

Purpose of the Study:

  • To investigate the role of hsa_circ_0005576 in osimertinib resistance in LUAD.
  • To elucidate the underlying molecular mechanism of hsa_circ_0005576-mediated resistance.

Main Methods:

  • knockdown of hsa_circ_0005576 in resistant LUAD cells.
  • Investigated proliferation, apoptosis, and sensitivity to osimertinib.
  • Conducted mechanistic studies involving miRNA sponging and target gene analysis (miR-512-5p/IGF1R).
  • Performed rescue assays to validate findings.

Main Results:

  • hsa_circ_0005576 knockdown suppressed proliferation and promoted apoptosis in osimertinib-resistant LUAD cells.
  • Knockdown of hsa_circ_0005576 increased LUAD cell sensitivity to osimertinib.
  • hsa_circ_0005576 acts as a sponge for miR-512-5p, upregulating its target, IGF1R.
  • Inhibition of miR-512-5p reversed the effects of hsa_circ_0005576 knockdown.

Conclusions:

  • hsa_circ_0005576 facilitates osimertinib resistance in LUAD by regulating proliferation and apoptosis via the miR-512-5p/IGF1R pathway.
  • hsa_circ_0005576 represents a potential therapeutic target for overcoming osimertinib resistance in LUAD.
  • This study provides novel insights into the molecular mechanisms of osimertinib resistance in LUAD.
Keywords:
IGF1Rhsa_circ_0005576lung adenocarcinomamiR-512-5posimertinib resistance

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