Overexpression of miR-101 promotes TRAIL-induced mitochondrial apoptosis in papillary thyroid carcinoma by targeting c-met and MCL-1

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) induces apoptosis in malignant cells, but not in normal cells. As papillary thyroid carcinoma cells broadly expressed TRAIL receptors (death receptor 4 and death receptor 5) on their surface, TRAIL is considered as a promising drug for treatment of papillary thyroid carcinoma. However, resistance to TRAIL still be a big obstacle to achieve a satisfactory effect for cancer therapy. Here, we found that overexpression of miR-101 was able to sensitize papillary thyroid carcinoma cells to TRAIL treatment in vitro and in vivo. Mechanically, we found that genes of c-met and MCL-1 were the targets of miR-101. Overexpression of miR-101 in TPC-1 significantly decreased the cellular protein levels of c-met and MCL-1, and thus inhibiting the PI3K/AKT pathway and reducing the resistance to TRAIL-induced mitochondrial apoptosis. Enforced expression of either c-met or MCL-1 could partially inhibit the miR-101 promoted apoptosis in TRAIL-treated TPC-1 cells. These results indicated that miR-101-c-met/MCL-1 axis determined the sensitivity of TRAIL to thyroid cancer in some extent. Combination with TRAIL and miR-101 may represent a novel approach to kill papillary thyroid carcinoma cells efficiently.