Antitumor Effect of miR-1294/Pyruvate Kinase M2 Signaling Cascade in Osteosarcoma Cells

Quan Yuan1, Honghao Yu1, Jianhua Chen1

  • 1Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.

Oncotargets and Therapy
|February 29, 2020
PubMed
Abstract

Insights

MicroRNA-1294 (miR-1294) is downregulated in osteosarcoma. Upregulating miR-1294 inhibits tumor growth by targeting pyruvate kinase M2 (PKM2), suggesting a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression implicated in cancer progression.
  • Osteosarcoma is a primary bone malignancy with significant metastatic potential.

Purpose of the Study:

  • To investigate the role of the miR-1294/pyruvate kinase M2 (PKM2) axis in osteosarcoma.
  • To evaluate miR-1294's function in osteosarcoma cell proliferation, migration, invasion, apoptosis, and tumorigenesis in vitro and in vivo.

Main Methods:

  • Real-time PCR, CCK-8 assays, Western blot, scratch tests, transwell assays, and flow cytometry were used to assess miR-1294 function in osteosarcoma cells.
  • Dual-luciferase reporter assays confirmed PKM2 as a direct target of miR-1294.
  • Subcutaneous xenograft models were employed to evaluate the in vivo effect of miR-1294 on tumor growth.

Main Results:

  • miR-1294 was found to be downregulated in osteosarcoma tissues and cells.
  • Overexpression of miR-1294 significantly inhibited osteosarcoma cell proliferation, migration, and invasion, while inducing apoptosis and cell cycle arrest.
  • PKM2 was identified as a direct target of miR-1294, and its overexpression reversed the inhibitory effects of miR-1294. In vivo studies showed that miR-1294 upregulation suppressed osteosarcoma tumorigenesis.

Conclusions:

  • The miR-1294/PKM2 signaling pathway plays a critical role in regulating osteosarcoma progression.
  • This pathway represents a promising therapeutic target for osteosarcoma treatment.

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