MicroRNA?126?3p suppresses HeLa cell proliferation, migration and invasion, and increases apoptosis via the PI3K/PDK1/AKT pathway.

ABSTRACT: We previously reported that relative to normal cervical mucus, microRNA 126?3p (miR?126?3p) is present in significantly greater amounts in the cervical mucus of patients with overt cervical cancer or precursor lesions. Here, we investigated the effects of enforced miR?126?3p expression in the cervical cancer cell line, HeLa, on proliferation, migration, invasion, apoptosis and protein expression. We transfected HeLa cells with miR?126?3p miRNA and found that proliferation, migration and invasion by cell counting, wound healing, cell migration and invasion assay were significantly reduced in these cells relative to those transfected with a negative control mimic. The levels of phosphoinositide 3 kinase (PI3K), phosphorylated 3?phosphoinositide?dependent protein kinase?1 (p?PDK1) and p?AKT proteins were lower in the miR?126?3p?transfected cells. Phosphorylated 70S6K (p?p70S6K), phosphorylated glycogen synthase kinase 3? (p?GSK3?), phosphorylated S6K (p?S6K), cyclin D1, phosphorylated p21?activated kinase 1 (p?PAK1), Rho associated coiled?coil containing protein kinase 1 (ROCK1), myotonic dystrophy?related CDC42?binding kinases ? (MRCK?) and phospholipase C ?1 (p?PLC?1) were also downregulated. This suggests that downstream effectors of the PI3K/PDK1/AKT pathway are targets for inhibition by miR?126?3p. In contrast, apoptotic?related proteins including the BCL?2?associated agonist of cell death (Bad), B?cell lymphoma?extra?large (Bcl?xL) and BCL?2?associated X (Bax), were all upregulated by miR?126?3p, resulting in increased caspase 3/7 activity and apoptosis. Thus, enforced expression of miR?126?3p inhibited cell migration and invasion and also induced apoptosis by regulating the PI3K/PDK1/AKT pathway in HeLa cells. Hence, high levels of miR?126?3p may inhibit cervical carcinogenesis, and targeting the PI3K/PDK1/AKT pathway via miR?126?3p could represent a new approach for treating patients with cervical cancer.

SUBMITTER: Ichikawa R 

PROVIDER: S-EPMC7057934 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature