MicroRNA-216b-3p inhibits lung adenocarcinoma cell growth via regulating PDZ binding kinase/T-LAK-cell-originated protein kinase.

Abstract

Numerous studies have reported that microRNA (miR)-216b, as a tumor suppressor, is downregulated in a variety of cancer types. PDZ binding kinase (PBK)/T-LAK-cell-originated protein kinase (TOPK) is highly expressed in various types of human cancer, including lung cancer. The expression of miR-216b-3p and its potential roles in lung adenocarcinoma are still unclear and no research has been conducted into the association between miR-216b-3p and PBK/TOPK. Thus, the present study aimed to investigate the expression and role of miR-216b-3p in lung adenocarcinoma and to explore whether PBK/TOPK is involved in the underlying mechanisms of lung adenocarcinoma. The expression of miR-216b-3p in lung adenocarcinoma cell lines was detected. PBK/TOPK protein expression levels were also determined within lung adenocarcinoma cell lines. To investigate the association between miR-216b-3p and PBK/TOPK, TargetScan analysis was performed; PBK was predicted to be a potential target gene of miR-216b-3p, and a dual luciferase reporter assay was applied to confirm this prediction. To investigate the role of miR-216b-3p in lung adenocarcinoma, a lung adenocarcinoma cell line (GLC-82) was transfected with miR-216b-3p mimic or its negative control. An MTT assay was applied to detect cell proliferation, and cell apoptosis was analyzed by flow cytometry. Western blot analysis was performed to determine the protein expression levels of associated proteins. The results of the present study suggested that miR-216b-3p was downregulated in lung adenocarcinoma cell lines and PBK/TOPK was highly expressed in lung adenocarcinoma cells. miR-216b-3p directly targets PBK and negatively regulates its expression. miR-216b-3p overexpression may inhibit GLC-82 cell proliferation and induce cell apoptosis. In addition, miR-216b-3p overexpression may increase p53 and p21 expression, and prevent p38 MAPK activation. These effects on GLC-82 cells caused by miR-216b-3p overexpression may be eliminated by PBK/TOPK overexpression. In conclusion, miR-216b-3p was downregulated in lung adenocarcinoma and may function as a tumor suppressor by inhibiting cell growth via regulating PBK/TOPK expression.