2. Academic Validation
  3. RUNDC3A-AS1 is an adverse prognostic factor for triple-negative breast cancer which mediates the Warburg effect and Adriamycin resistance by targeting miR-224-3p/COL5A2

RUNDC3A-AS1 is an adverse prognostic factor for triple-negative breast cancer which mediates the Warburg effect and Adriamycin resistance by targeting miR-224-3p/COL5A2

  • Toxicol Appl Pharmacol. 2026 Jun:511:117776. doi: 10.1016/j.taap.2026.117776.
Linna Kong 1,  Xiaoyan Liu 1,  Huihui Zhang 1,  Jiaqi Liu 2
Affiliations

Affiliations

  • 1 Department of Breast and Thyroid Surgery, Zibo Central Hospital, Zibo 255020, China.
  • 2 Department of Breast and Thyroid Surgery, Zibo Central Hospital, Zibo 255020, China. Electronic address: [email protected].
PMID: 41765289 DOI: 10.1016/j.taap.2026.117776
Abstract

Breast Cancer has become the most common malignant tumor among women worldwide, among which triple-negative breast Cancer (TNBC) is a subtype with the worst prognosis. Although the function of long non-coding RNA (lncRNA) RUNDC3A-AS1 in Other cancers has been revealed, it has not been reported in TNBC. To explore the functional mechanism of RUNDC3A-AS1 in TNBC by regulating miR-224-3p/COL5A2, the predictive value of RUNDC3A-AS1 for disease prognosis was evaluated by using its serum level in TNBC patients. miR-224-3p/COL5A2, as a potential downstream of RUNDC3A-AS1, was predicted by the lncRNASNP-human and miRDB databases. Their binding relationships were verified through RNA pull-down experiment. The function of this signaling axis in aerobic glycolysis of TNBC cells was evaluated by detecting glucose uptake, ATP production, and extracellular acidification rate (ECAR). The Adriamycin (ADR)-resistant TNBC cell lines were introduced to explore the function of RUNDC3A-AS1/miR-224-3p/COL5A2 axis in chemotherapy resistance. TNBC patients with high RUNDC3A-AS1 expression showed lower survival rates and shorter overall survival time. RUNDC3A-AS1 competed with COL5A2 mRNA in binding to miR-224-3p, and it increased COL5A2 expression by negatively regulating miR-224-3p. The overexpression of RUNDC3A-AS1 promoted aerobic glycolysis in TNBC cells, which was reversed by the miR-224-3p agonist. Meanwhile, COL5A2 overexpression reversed the inhibitory function of miR-224-3p agonist on aerobic glycolysis. Silencing RUNDC3A-AS1/COL5A2 or upregulating miR-224-3p reduced lactic acid production in ADR-resistant cells and increased their sensitivity to ADR. In conclusion, as a Sponge of miR-224-3p, RUNDC3A-AS1 mediated the Warburg effect and chemotherapy resistance in TNBC by up-regulating COL5A2.

Keywords

Adriamycin; COL5A2; RUNDC3A-AS1; Triple-negative breast cancer; Warburg effect; miR-224-3p.

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