Targeting the splicing factor hnRNP M with an endogenous circular RNA aptamer suppresses cancer metastasis

However, therapeutic strategies to reprogram pathological AS networks remain limited. Here, we identified a circular RNA, MASCOT (hnRNP M-ASsociated Circular RNA Of TGFβ), that functions as an endogenous aptamer targeting the splicing factor hnRNP M, a central regulator of EMT-related AS reprogramming.

As an endogenous repressor of hnRNP M, MASCOT maintains the epithelial status of cancer cells and suppresses tumor metastasis. Conversely, its downregulation by TGFβ releases hnRNP M to initiate EMT-associated splicing changes. Restoring MASCOT expression significantly reduces metastatic burden in mouse models.