MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2

Baoen Jiang1, Weidong Mu2, Jiangquan Wang3

  • 1Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China. baoen_jiang@163.com.

Abstract

Insights

MicroRNA-138 (miR-138) is downregulated in osteosarcoma, acting as a tumor suppressor. It inhibits cancer progression by targeting DEC2, suggesting a new therapeutic strategy for osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • MicroRNA-138 (miR-138) is recognized as a tumor suppressor in various cancers.
  • The specific role and expression of miR-138 in human osteosarcoma remain largely uncharacterized.
  • This study aimed to elucidate the function and regulatory mechanisms of miR-138 in osteosarcoma.

Purpose of the Study:

  • To investigate the expression levels of miR-138 in human osteosarcoma tissues and cell lines.
  • To determine the functional role of miR-138 in osteosarcoma cell progression, including proliferation, apoptosis, and invasion.
  • To identify the molecular mechanism underlying miR-138's function, specifically its interaction with differentiated embryonic chondrocyte gene 2 (DEC2).

Main Methods:

  • Real-time PCR was used to quantify miR-138 expression in osteosarcoma samples and cell lines.
  • Gain-of-function and loss-of-function experiments were conducted to assess miR-138's impact on cell behavior.
  • Cell proliferation, apoptosis, and invasion assays (MTT, flow cytometry, transwell-matrigel) were employed.
  • Dual-luciferase reporter assays confirmed DEC2 as a direct target of miR-138.

Main Results:

  • MiR-138 expression was significantly reduced in osteosarcoma tissues and cell lines compared to normal controls.
  • Lower miR-138 levels correlated with metastatic status in osteosarcoma.
  • Overexpression of miR-138 suppressed proliferation and invasion while promoting apoptosis in osteosarcoma cells.
  • DEC2 was identified as a direct target, and its inhibition by miR-138 was crucial for the observed anti-tumor effects.

Conclusions:

  • MiR-138 functions as a tumor suppressor in human osteosarcoma.
  • MiR-138 inhibits osteosarcoma cell proliferation and invasion and promotes apoptosis, partly through the downregulation of DEC2.
  • The miR-138/DEC2 axis represents a potential novel therapeutic target for osteosarcoma treatment.

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