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MiR-451a promotes cell growth, migration and EMT in osteosarcoma by regulating YTHDC1-mediated m6A methylation to

Dong Cao1, Shanshan Ge1, Mengchun Li2

  • 1The Physical Examination Center, First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.

Journal of Bone Oncology
|February 24, 2022
PubMed
Abstract

Insights

MicroRNA-451a (miR-451a) inhibits osteosarcoma progression by regulating YTHDC1-mediated m6A methylation. This mechanism activates the AKT/mTOR pathway, promoting malignancy in osteosarcoma cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Osteosarcoma is a primary malignant bone tumor with a poor prognosis.
  • The AKT/mammalian target of rapamycin (mTOR) signaling pathway is crucial in cellular processes and a target for anti-tumor therapies.

Purpose of the Study:

  • To investigate the role of microRNA-451a (miR-451a) in osteosarcoma.
  • To elucidate the mechanism by which miR-451a affects osteosarcoma malignancy and the AKT/mTOR pathway.

Main Methods:

  • Quantitative real-time polymerase chain reaction (q-PCR) and western blot analyses were used to detect RNA and protein levels.
  • Functional assays assessed osteosarcoma cell malignancy.
  • RNA-binding protein immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP), RNA pulldown, luciferase reporter, and in vitro kinase assays were employed to determine the mechanism.

Main Results:

  • miR-451a was found to repress the malignant progression of osteosarcoma.
  • miR-451a inhibits the AKT/mTOR pathway through 3-phosphoinositide dependent protein kinase 1 (PDPK1)-mediated phosphorylation.
  • YTH domain containing 1 (YTHDC1) regulates the m6A phosphorylation of PDPK1 mRNA, and miR-451a stabilizes PDPK1 mRNA via YTHDC1 and m6A-dependent regulation.

Conclusions:

  • miR-451a plays a critical role in suppressing osteosarcoma malignancy.
  • The study reveals a novel mechanism involving miR-451a, YTHDC1, m6A methylation, and the AKT/mTOR pathway in osteosarcoma.
  • Understanding this pathway could lead to new therapeutic strategies for osteosarcoma.
Keywords:
AKT/mTOR signaling pathwayANOVA, Analysis of varianceCdna, Complementary DNAGEO, Gene Expression OmnibusOsteosarcomaPDPK1, 3-phosphoinositide dependent protein kinase 1RIP, Co-IP, Co-immunoprecipitationSD, Standard deviationYTHDC1, YTH domain containing 1m6A methylationmTOR, Mammalian target of rapamycinmiR-451amiR-451a, MicroRNA-451aq-PCR, Quantitative real-time polymerase chain reaction

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