Chai Yaqin, Xue Huijun, Wu Yanmei, Du Xiaomei, Zhang Zhuohong, Zhang Yinliang, Zhang Lili, Zhang Shuanbao, Zhang Zhiguo, Xue Zhiwen
Department of Respiratory Medicine, Xi'an XD Group Hospital, Xi'an, Shaanxi 710077, P.R. China.
Department of Respiratory Medicine, Xijing Hospital, Xi'an, Shaanxi 710032, P.R. China.
Exp Ther Med. 2018 Jun;15(6):4822-4828. doi: 10.3892/etm.2018.6020. Epub 2018 Apr 2.
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.
大量研究报道，作为一种肿瘤抑制因子，微小RNA（miR）-216b在多种癌症类型中表达下调。PDZ结合激酶（PBK）/T淋巴细胞激活的杀伤细胞源蛋白激酶（TOPK）在包括肺癌在内的多种人类癌症中高表达。miR-216b-3p在肺腺癌中的表达及其潜在作用仍不清楚，且尚未有关于miR-216b-3p与PBK/TOPK之间关联的研究。因此，本研究旨在探讨miR-216b-3p在肺腺癌中的表达及作用，并探究PBK/TOPK是否参与肺腺癌的潜在机制。检测了miR-216b-3p在肺腺癌细胞系中的表达。还测定了肺腺癌细胞系中PBK/TOPK蛋白的表达水平。为研究miR-216b-3p与PBK/TOPK之间的关联，进行了TargetScan分析；预测PBK是miR-216b-3p的潜在靶基因，并应用双荧光素酶报告基因检测来证实这一预测。为研究miR-216b-3p在肺腺癌中的作用，用miR-216b-3p模拟物或其阴性对照转染肺腺癌细胞系（GLC-82）。应用MTT法检测细胞增殖，并通过流式细胞术分析细胞凋亡。进行蛋白质印迹分析以确定相关蛋白的表达水平。本研究结果表明，miR-
