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miR-216a-3p 通过下调 ACTL6A 介导的 YAP 信号通路抑制宫颈癌的增殖和侵袭。

MiR-216a-3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A-mediated YAP signaling.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

出版信息

J Cell Physiol. 2020 Dec;235(12):9718-9728. doi: 10.1002/jcp.29783. Epub 2020 May 13.

Abstract

The tumor-suppressive role of microRNA-216a-3p (miR-216a-3p) has been evidenced in multiple tumors. Yet, the relevance of miR-216a-3p in cervical cancer remains undermined. The current study was designed to determine the expression and potential function of miR-216a-3p in cervical cancer. Expression of miR-216a-3p was markedly decreased in cervical cancer and functional assays revealed an inhibitory effect of miR-216a-3p on the proliferation, colony formation, and invasion of cervical cancer. Actin-like 6A (ACTL6A) was identified as a target gene of miR-216a-3p. Elevated ACTL6A expression was detected in cervical cancer, and ACTL6A inhibition exhibited a tumor-suppressive effect. ACTL6A inhibition increased yes-associated protein (YAP) phosphorylation and downregulated YAP-mediated transcriptional activity. ACTL6A restoration or YAP reactivation partially abrogated the miR-216a-3p-mediated antitumor effect in cervical cancer cells. Taken together, these data demonstrate that miR-216a-3p acts as a potential tumor-suppressive miRNA in cervical cancer, which exerts its function through inhibition of YAP signaling via targeting ACTL6A.

摘要

miR-216a-3p(miR-216a-3p)在多种肿瘤中具有肿瘤抑制作用。然而,miR-216a-3p 在宫颈癌中的相关性仍未得到证实。本研究旨在确定 miR-216a-3p 在宫颈癌中的表达和潜在功能。miR-216a-3p 在宫颈癌中的表达明显降低,功能分析显示 miR-216a-3p 对宫颈癌的增殖、集落形成和侵袭具有抑制作用。肌动蛋白样 6A(ACTL6A)被鉴定为 miR-216a-3p 的靶基因。在宫颈癌中检测到 ACTL6A 表达升高,ACTL6A 抑制表现出肿瘤抑制作用。ACTL6A 抑制增加了 yes 相关蛋白(YAP)磷酸化,并下调了 YAP 介导的转录活性。ACTL6A 恢复或 YAP 再激活部分消除了 miR-216a-3p 在宫颈癌细胞中的抗肿瘤作用。总之,这些数据表明,miR-216a-3p 在宫颈癌中作为一种潜在的肿瘤抑制 miRNA 发挥作用,通过靶向 ACTL6A 抑制 YAP 信号通路发挥其功能。

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