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A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
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C1QTNF1-AS1/miR-346 axis suppresses osteosarcoma progression via dual inhibition of LDHA/PDK1-mediated Warburg effect

Yu Zhang1,2,3, Jingyi Hou1, Kaikai Ding1,2,3

  • 1Graduate School of Chengde Medical University, Chengde, Hebei, 067000, China.

BMC Cancer
|November 4, 2025
PubMed
Abstract

Insights

A novel regulatory axis involving C1QTNF1-AS1 and miR-346 was identified in osteosarcoma (OS). This axis targets key glycolytic enzymes, offering a new therapeutic strategy to combat OS metabolism and chemotherapy resistance.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Osteosarcoma (OS) exhibits aggressive growth and chemoresistance, largely driven by the Warburg effect.
  • Current strategies to target this metabolic adaptation in OS are limited.
  • Understanding noncoding RNA regulation of the Warburg effect is crucial for developing new therapies.

Purpose of the Study:

  • To identify novel noncoding RNA regulatory mechanisms governing the Warburg effect in OS.
  • To explore the C1QTNF1-AS1/miR-346 axis as a potential therapeutic target for OS metabolism.
  • To investigate the impact of this axis on OS cell proliferation, migration, and invasion.

Main Methods:

  • Integrated bioinformatics analysis of GEO dataset GSE126209.
  • Experimental validation using qPCR, Western blotting, and dual-luciferase assays.
  • Functional assays including cell proliferation, migration, invasion, and metabolic measurements (glucose, lactate, ATP).

Main Results:

  • A novel regulatory axis: long noncoding RNA C1QTNF1-AS1/microRNA-346 (miR-346)/pyruvate dehydrogenase kinase 1 (PDK1)-lactate dehydrogenase A (LDHA) was identified.
  • miR-346 suppressed PDK1 and LDHA, while C1QTNF1-AS1 enhanced their activity.
  • This interaction induced a metabolic crisis in OS cells, reducing lactate production and reversing chemoresistance.

Conclusions:

  • The C1QTNF1-AS1/miR-346 axis represents a druggable vulnerability in osteosarcoma metabolism.
  • miR-346 shows potential as a multitarget RNA therapeutic to inhibit the Warburg effect.
  • This axis offers a novel strategy for metabolic intervention in osteosarcoma treatment.
Keywords:
C1QTNF1-AS1LDHAMiR-346PDK1Warburg effect

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