MicroRNA-488-3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma
MicroRNA-488-3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma
复制标题
MicroRNA-488-3p通过靶向ZBTB2抑制食管鳞状细胞癌的增殖和诱导凋亡
DOI：
10.1002/jcb.29178
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发表时间：
2019-11-01
影响因子：
4
通讯作者：
Lin, Xiaoming
中科院分区：
文献类型：
--
作者：
Yang, Yi;Li, He;Lin, Xiaoming
食道鳞状细胞癌(ESCC)是第八位最常见的癌症，也是癌症相关死亡的第六大原因。越来越多的研究表明，microRNAs(MiRNAs)通过调节某些基因的表达在人类癌症中发挥重要的调节功能。MIR-488-3P已被证实在多种癌症中是一种肿瘤抑制因子，但其在ESCC中的作用尚不清楚。本研究旨在揭示miR-488-3p在食管癌中的生物学作用及其调控机制。我们首次揭示了miR-488-3p在ESCC组织和细胞系中的下调。功能获得分析证实，miR-488-3p过表达抑制细胞增殖，促进细胞凋亡。从机制上，我们通过生物信息学工具进行了鉴定，证实了含有2的锌指和BTB结构域(ZBTB2)是miR-488-3p的靶点。此外，miR-488-3p通过抑制ZBTB2激活P53通路。救援性实验证明，ZBTB2参与了miR-488-3p对ESCC细胞增殖和凋亡的调控。此外，我们还证实了miR-488-3p参与miR-488-3p对ESCC的调控，从而证实了miR-488-3p在ESCC中有不同的靶点。综上所述，本研究揭示了miR-488-3p通过靶向ZBTB2和激活P53通路抑制食管鳞癌的增殖和诱导细胞凋亡，为食管鳞癌提供了一个新的生物学靶点。
Esophageal squamous cell carcinoma (ESCC) is the eighth most prevalent cancer and the sixth leading cause for cancer-associated mortality. MicroRNAs (miRNAs) are increasingly reported to exert important regulatory functions in human cancers by regulating certain gene expression. miR-488-3p has been identified to be a tumor suppressor in multiple cancers, but its role in ESCC is yet to be investigated. The present study aimed to uncover the biological role and modulatory mechanism of miR-488-3p in ESCC. We first revealed the downregulation of miR-488-3p in ESCC tissues and cell lines. Gain-of-function assays confirmed that miR-488-3p overexpression abrogated proliferation and accelerated apoptosis. Mechanistically, we identified via bioinformatics tool and confirmed that zinc finger and BTB domain containing 2 (ZBTB2) was a target for miR-488-3p. Moreover, miR-488-3p activated the p53 pathway through suppressing ZBTB2. Finally, rescue assays proved that ZBTB2 was involved in the regulation of miR-488-3p on proliferation and apoptosis in ESCC. Additionally, we verified that miR-488-3p had alternate targets in ESCC by confirming the involvement of protein kinase, DNA-activated, catalytic subunit (PRKDC), a known target for miR-488-3p, in miR-488-3p-mediated regulation on ESCC. In sum, this study revealed that miR-488-3p inhibited proliferation and induced apoptosis by targeting ZBTB2 and activating p53 pathway in esophageal squamous cell carcinoma, providing a novel biological target for ESCC.