Muscleblind‑like 1 destabilizes Snail mRNA and suppresses the metastasis of colorectal cancer cells via the Snail/E‑cadherin axis

Abstract

RNA-binding proteins (RBPs) play a fundamental roleintherecurrenceandmetastasisofcolorectalcancer(CRC). Inthisstudy,weidentifiedmuscleblind‑like1(MBNL1),anRBP implicated in developmental control, as a robust suppressor of CRC cell metastasis in vitro. By using a scratch assay coupled with time‑lapse live cell imaging, our findings revealed that the knockdown of MBNL1 induced epithelial‑to‑mesenchymal transition (EMT)‑like morphological changes in the HCT‑116 cells, accompanied by an enhanced cell motility, and by the downregulation of E-cadherin and the upregulation of Snail expression. By contrast, the ectopic overexpression of MBNL1 suppressed EMT, characterized by the upregulation of E-cadherin and the downregulation of Snail expression. Mechanistically, Snail rather than E‑cadherin, was identified as a direct downstream target gene of MBNL1. The ectopic the overexpression of MBNL1 markedly enhanced the recruitment of Snail transcripts to processing bodies (P-bodies), leading to the increased degradation of Snail mRNA and consequent translational silencing. Furthermore, the effect of MBNL1 on CRC cell migration was confirmed in additional CRC cell lines. SW480 and HT‑29 cells exhibited similar changes in migratory capacity and the expression of Snail/E-cadherin to those observed in HCT‑116 cells. On the whole, this study demonstrates that MBNL1 destabilizes Snail transcripts and, in turn, suppresses the EMT of CRC cells through the Snail/E-cadherin axis in vitro. Therefore, this EMT‑related MBNL1/Snail/E-cadherin axis may prove to be a novel therapeutic target for CRC metastasis.