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. 2025 Jun 25;42(8):280.
doi: 10.1007/s12032-025-02836-9.

lnc-MTRNR2L12-3 derived from hypoxic breast cancer cell exosomes facilitates angiogenesis via the Src/FAK signaling pathway

Li Zheng #  1 , Juanfen Mo #  1 , Xuesong He #  1 , Qi Xu  2 , Yi Bao  1 , Jiayuan Wu  3
Affiliations

lnc-MTRNR2L12-3 derived from hypoxic breast cancer cell exosomes facilitates angiogenesis via the Src/FAK signaling pathway

Li Zheng et al. Med Oncol. .

Abstract

Exosomal long non-coding RNAs (lncRNAs) play crucial roles in breast cancer progression. However, the mechanisms by which hypoxia-induced exosomes mediate angiogenesis through lncRNAs in the tumor microenvironment remain largely unexplored. In this study, exosomes were isolated and characterized from MDA-MB-231 breast cancer cells under normoxic and hypoxic conditions. Hypoxia-induced exosomes (Hyp-exo) were shown to significantly promote angiogenesis. Microarray analysis revealed that lnc-MTRNR2L12-3 was highly enriched in Hyp-exo compared to normoxic exosomes (NC-exo). Functional studies, both in vitro and in vivo, demonstrated that exosomal lnc-MTRNR2L12-3 derived from hypoxic breast cancer cells substantially enhanced angiogenesis. Mechanistically, PCR array and western blot analysis confirmed that silencing lnc-MTRNR2L12-3 inhibited Src/FAK signaling pathway activation in HUVECs, while hypoxia-induced exosomes effectively rescued this suppression. Overall, hypoxia-induced breast cancer exosomes deliver lnc-MTRNR2L12-3 to endothelial cells, promoting angiogenesis through the Src/FAK signaling pathway. These findings provide new insights into targeting angiogenesis in the tumor microenvironment for breast cancer therapy.

Keywords: Angiogenesis; Breast cancer; Exosome; Hypoxia; Lnc-MTRNR2L12-3; Src/FAK signaling pathway.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All protocols involving animal experiments were proved strictly by Medical Ethics Committee of the Second Affiliated Hospital of Jiaxing University. The study was conducted in accordance with the local legislation and institutional requirements.

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