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

Abstract

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.

LINC00623/miR-101/HRAS axis modulates IL-1β-mediated ECM degradation, apoptosis and senescence of osteoarthritis chondrocytes

“…More importantly, although its role in OA has rarely been reported, miR-101 is well-known for its tumor suppressive function. By promoting cancer cell apoptosis, miR-101 can serve as a tumor suppressor [47][48][49]. In nasopharyngeal carcinoma cells, miR-101 exerted its apoptosis-promoting function by inhibiting the Ras/Raf/MEK/ERK signaling pathway [47].…”

miR‐199b‐5p‐Stonin 2 axis regulates metastases and epithelial‐to‐mesenchymal transition of papillary thyroid carcinoma

“…Although many achievements have been made in thyroid carcinoma treatment, the survival, and existence of patients remain unsatisfactory (3). Because of the few clinical indications, most patients are diagnosed only in the late stage and have little probability to obtain efficient and helpful treatment (4). Therefore, the exploration of new cancer-specific biomarkers will lead to clinical therapy and improve the patient diagnosis.…”

MicroRNA-101 Targets CXCL12-Mediated Akt and Snail Signaling Pathways to Inhibit Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma

“…Zhao et al 19 reported that miR-101 reduces PTC cell proliferation, apoptosis resistance, migration, and invasion in vitro and suppresses tumor growth and metastasis in vivo by targeting USP22. miR-101 was able to sensitize PTC cells to TRAIL treatment in vitro and in vivo through driving TRAIL-induced mitochondrial apoptosis by targeting c-met and MCL-1 20 . Consistently, in this study, we demonstrated that miR-101 was pronouncedly downregulated in PTC tissues and cell lines.…”

“…In the literature, miRNA-101 (miR-101) affords tumor-suppressive roles in a variety of human malignancies, such as breast cancer 12 , colon cancer 13 , lung cancer 14 , hepatocellular carcinoma 15 , gastric cancer 16 , and PTC 17–20 . Reportedly, miR-101 inhibits PTC cell proliferation, migration, and invasion by targeting Rac1 17,18 , hinders tumorigenesis of PTC in vitro and in vivo by downregulating USP22 19 , and promotes TRAIL-induced mitochondrial apoptosis of PTC cells by targeting c-met and Mcl-1 20 . However, knowledge is limited on the mechanisms by which miR-101 reduces the vicious behaviors of PTC.…”