SOCS (Suppressor of Cytokine-induced Signaling) proteins consist of eight members and share a central src homology 2 domain (SH2), a C-terminal SOCS box and unique N-termini. Members of the SOCS family are negative regulators of STAT signaling pathways. Recent years, the SOCS family is found to play important roles in cancer, but there are still many functions and mechanisms need to be further explored. The down-expression of SOCS2 has been found in solid organ malignancies, such as colorectal cancer, breast cancer, lung cancer and liver cancer. Our preliminary microarray data showed that 31 (77.5%) of 40 oral cancer patients have lower SOCS2 expression profile. Meanwhile, miRNAs are 21−24 bases non-coding RNA that regulate gene expression either by degrading target mRNAs or by inhibiting their translation. We use microRNA.org and miRNAmap database to predict the putative miRNAs that can target SOCS2. We found that miR-424−5p is the only one of overlapping miRNA predicted from these two databases. And we confirmed this finding by transfection of miRNA mimic and by 3 UTR reporter assay. We also found miR-424−5p inhibitor could increase expression of SOCS2 protein and inhibits STAT5 activation in oral cancer cells. In addition, we found that overexpression of miR-424−5p could promote cell migration, invasion and STAT5 activation via downregulation of SOCS2. Taken together, our results identify a novel mechanism for mir-424−5p-mediated progression of oral cancer and establish a functional link between mir-424−5p, SOCS2, and STAT5 signaling pathway. Furthermore, we found that IL8 increased miR-424−5p expression, which activated STAT5 pathways through suppressing SOCS2 expression.
日期:
2014-11
關聯:
European Journal of Cancer. 2014 Nov;50(Suppl. 6):147.
