MicroRNA-335 targets the MEK/ERK pathway to regulate the proliferation and metastasis of colon cancer.

Several studies have proved the tumor-suppressive effects of miR-335 but its role in colon cancer via regulation of the Raf/MEK/ERK signalling pathway is yet unknown. As such the main motive of conducting the present study was to elucidate the role of miR-335 in colon cancer via regulation of Raf/MEK/ERK signalling pathway and to explore its therapeutic potential. The results revealed significant (P < 0.05) downregulation of miR-335 in colon cancer and its overexpression led to a significant (P < 0.05) decline in viability of the HT-29 and SW948 cells. The TUNNEL assay showed miR-335 promotes apoptosis in the HT-29 and SW948 colon cancer cells and is also associated with increase in Bax and decrease in Bcl-2 expression. The results also revealed that miR-335 overexpression enhances the sensitivity of the HT-29 and SW948 cells to the apoptotic effects of cisplatin. From the transwell assays, it was found that the migration of the HT-29 and SW948 cells was decreased by 53% and 45% and while as invasion was decreased by 49% and 42% respectively (P < 0.05). Finally, western blot analysis showed that miR-335 blocks the Raf/MEK/ERK signalling pathway in HT-29 colon cancer cells. The results of in vivo study showed that miR-335 also exhibits tumor-suppressive effects on xenografted tumors. Taken together, it is concluded that miR-335 acts as tumor-suppressor in colon cancer and may exhibit therapeutic implications in its treatment. AJTR