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MicroRNA-374b-5p suppresses osteosarcoma progression via the PDPK1-mediated AKT pathway

Yong Xi1,2, Zhengyi Sun1, Jingbin Wu1

  • 1Department of Orthopedics, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, China.

Translational Cancer Research
|February 12, 2026
PubMed
Abstract

Insights

MicroRNA-374b-5p (miR-374b-5p) is downregulated in osteosarcoma (OS). Upregulating miR-374b-5p inhibits OS progression by targeting PDPK1 and suppressing the AKT pathway.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) regulate gene expression and are implicated in various biological processes.
  • Previous research suggests a potential anti-tumor role for microRNA-374b-5p (miR-374b-5p) in several cancers.
  • Osteosarcoma (OS) is a primary bone malignancy with complex molecular underpinnings.

Purpose of the Study:

  • To investigate the functional role of miR-374b-5p in osteosarcoma (OS) progression.
  • To elucidate the underlying molecular mechanisms by which miR-374b-5p influences OS development.
  • To assess the therapeutic potential of targeting miR-374b-5p in osteosarcoma.

Main Methods:

  • Bioinformatic analysis of the GSE65071 dataset (GEO database) to identify differentially expressed miRNAs.
  • Validation of miR-374b-5p expression in OS tissues and cell lines using qRT-PCR and FISH.
  • In vitro assays including CCK-8, colony formation, Transwell, and flow cytometry to evaluate OS cell proliferation, migration, invasion, and apoptosis.
  • Mechanism studies involving qRT-PCR, dual-luciferase reporter assay, and western blotting.
  • In vivo evaluation using a nude mice xenograft tumor model.

Main Results:

  • miR-374b-5p expression was significantly downregulated in osteosarcoma (OS) tissues and cell lines.
  • Overexpression of miR-374b-5p inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis.
  • Mechanism studies revealed that miR-374b-5p directly targets phosphoinositide-dependent protein kinase 1 (PDPK1), suppressing the AKT signaling pathway.
  • PDPK1 was highly expressed in OS and its silencing inhibited OS progression.
  • Overexpression of PDPK1 partially reversed the inhibitory effects of miR-374b-5p on OS progression both in vitro and in vivo.

Conclusions:

  • miR-374b-5p acts as a tumor suppressor in osteosarcoma (OS).
  • The upregulation of miR-374b-5p inhibits OS progression by directly targeting PDPK1 and modulating the AKT pathway.
  • miR-374b-5p represents a potential therapeutic target for osteosarcoma treatment.
Keywords:
AKTmiR-374b-5posteosarcoma (OS)phosphoinositide-dependent protein kinase 1 (PDPK1)

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