Triple‑negative breast cancer cell‑derived piR‑31115 promotes the proliferation and migration of endothelial cells via METTL3‑mediated m6A modification of YAP1.

Abstract

Triple‑negative breast cancer (TNBC), a highly malignant breast cancer subtype with a pronounced metastatic propensity, forms the focus of the present investigation. MDA‑MB‑231, a prevalently utilized TNBC cell line in cancer research, was employed. In accordance with the tumour angiogenesis theory, cancer cells are capable of instigating angiogenesis and the formation of a novel vascular system within the tumour microenvironment, which subsequently sustains malignant proliferation and metastasis. Consequently, impeding the growth of tumour blood vessels holds substantial significance in suppressing TNBC metastasis. Piwi‑interacting RNAs (piRNAs), a category of endogenous non‑coding RNAs, have been demonstrated to modulate cancer progression. However, studies regarding the role of piRNAs in regulating angiogenesis within cancer cells are relatively scant. In the present study, via cell co‑culture experiments, it was revealed that piR‑31115 (a kind of piRNA) in MDA‑MB‑231 cells notably enhanced the recruitment of a human microvascular endothelial cell line (HMEC‑1). Moreover, the conditioned medium (CM, which was obtained from MDA‑MB‑231 cells via a specific culturing methodology and was employed for the subsequent treatment of HMEC‑1 cells to explore its impacts on the biological behaviors such as the proliferation and migration of HMEC‑1 cells) derived from MDA‑MB‑231 cells with upregulated piR‑31115 expression stimulated the proliferation and migration of HMEC‑1 cells. These findings suggest that piR‑31115 in MDA‑MB‑231 cells may play a pivotal role in modulating tumour angiogenesis. Further studies disclosed that the CM from MDA‑MB‑231 cells augmented the N6‑methyladenosine (m6A) RNA modification level via METTL3 in HMEC‑1 cells. Transcriptome sequencing revealed that METTL3 functions as an m6A writer protein for Yes‑associated protein 1 (YAP1), which exerts a positive influence on promoting the proliferation and migration of HMEC‑1 cells. Concurrently, the IGF2BP plays a crucial role in stabilizing YAP1 protein expression. Collectively, the present findings identified a signalling pathway through which MDA‑MB‑231 cells induce HMEC‑1 cell proliferation and migration by regulating m6A RNA methylation.