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miR-129-2 upregulation induces apoptosis and promotes NSCLC chemosensitivity by targeting SOX4

Weizheng Zhou1, Chengliang Cai1, Jie Lu1

  • 1Department of Cardiothoracic Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.

Thoracic Cancer
|February 11, 2022
PubMed
Abstract

Insights

MicroRNA-129-2 (miR-129-2) is downregulated in non-small-cell lung cancer (NSCLC). Upregulating miR-129-2 induces apoptosis and enhances chemosensitivity by targeting SOX4, offering a potential therapeutic strategy for NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality globally.
  • Current NSCLC treatments often yield unsatisfactory outcomes, necessitating novel therapeutic targets.

Purpose of the Study:

  • To investigate the role of miR-129-2 in non-small-cell lung cancer (NSCLC) cell apoptosis.
  • To explore the impact of miR-129-2 on NSCLC chemosensitivity.

Main Methods:

  • Utilized NSCLC cell lines (A549, NCl-H23, HCC827) and normal lung cells (BEAS-2B).
  • Examined miR-129-2 expression in NSCLC tissues and cell lines.
  • Verified SOX4 as a direct target of miR-129-2 using luciferase reporter assays and real-time PCR.
  • Assessed the effect of miR-129-2 upregulation on NSCLC xenograft models and cisplatin-resistant cell lines (A549/DDP).

Main Results:

  • miR-129-2 expression was significantly downregulated in NSCLC tissues and cell lines (NCl-H23, A549).
  • Upregulation of miR-129-2 promoted apoptosis in NCl-H23 and A549 cells and inhibited tumor growth in vivo.
  • miR-129-2 upregulation enhanced cisplatin sensitivity in the A549/DDP cell line, linked to SOX4 downregulation.
  • SOX4 was identified as a direct target gene of miR-129-2.

Conclusions:

  • miR-129-2 functions as a tumor suppressor in NSCLC.
  • Restoring miR-129-2 expression induces apoptosis and chemosensitivity in NSCLC by regulating SOX4.
  • miR-129-2 represents a promising diagnostic biomarker and therapeutic target for NSCLC treatment.
Keywords:
NSCLCSOX4cisplatinmiR-129-2target

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