Microcystin-LR promotes migration via the cooperation between microRNA-221/PTEN and STAT3 signal pathway in colon cancer cell line DLD-1.

Abstract Previous researches have reported that microcystin-LR (MC-LR) contributes to the progression of multiple types of carcinomas including colon cancer; however, the underlying molecular mechanisms remain unclear and require in-depth investigation. Here, the colon cell line DLD-1 was arranged for the analysis by the microRNA microarray which was associated with the cancer metastasis after MC-LR exposure. 31 human microRNAs were differentially expressed, including miR-221, which targeted 3′-UTR of PTEN mRNA and PTEN level was down-regulated by MC-LR treatment. Besides, MC-LR also induced the phosphorylation of STAT3, which can be reversed by adding miR-221 inhibitor and PTEN expression plasmid. Furthermore, miR-221 inhibitor, STAT3 siRNA and PTEN expression plasmid could reverse the effects of MC-LR induced migration with the accumulation of β-catenin in nuclei. In conclusion, our study suggested that MC-LR promoted the progression of colon carcinoma, at least in part, by regulating the expression miR-221, PTEN and STAT3 phosphorylation, which offers a novel perspective to understand the connection between MC-LR and colon cancer. Graphical abstract fx1 Highlights • MC-LR inhibits PTEN expression by up-regulating the level of miR-221. • MC-LR induces the phosphorylation of STAT3, which can be reversed by miR-221/PTEN. • PTEN and STAT3 suppress MC-LR-induced accumulation of β-catenin in nuclei. • MiR-221/PTEN and STAT3 signal pathway regulates the MC-LR-induced migration. [ABSTRACT FROM AUTHOR]