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miR-1179 在宫颈癌中下调,其过表达通过靶向 CHAF1A/ZEB1 抑制癌细胞侵袭。

MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1.

机构信息

Department of Obstetrics and Gynaecology, The No.2 People's Hospital of Hefei, Hefei, Anhui Province, 230011, China.

School of Economics and Finance, School of Economics and Finance, Xi'an Jiaotong University, Xi'an, Shaanxi Province,710061, China.

出版信息

Acta Biochim Pol. 2021 Mar 19;68(2):193-199. doi: 10.18388/abp.2020_5499.

DOI:10.18388/abp.2020_5499
PMID:33740340
Abstract

The anticancer effect of miR-1179 has been extensively studied in many tumors. The mechanism of miR-1179 action in cervical cancer, however, remains largely unknown. In the present study, miR-1179 was downregulated in both cervical cancer cell lines and cancer tissues. In addition, miR-1179 mimic suppressed cancer cells invasion and epithelial-mesenchymal transition (EMT) in cervical cancer SiHa and Caski cells. We found that chromatin assembly factor 1 subunit A (CHAF1A) might be a direct target of miR-1179 and could be regulated by miR-1179. Furthermore, CHAF1A shRNA suppressed the cervical cancer cells invasion and the expression of EMT-promoted proteins. Reversely, CHAF1A overexpression not only promoted cervical cancer cells invasion but also upregulated the level of Zinc finger E-box binding protein 1 (ZEB1), an EMT-related protein. The induction of ZEB1 could be counteracted by miR-1179 overexpression. It was observed that in cervical cancer patients' tissues, miR-1179 was downregulated while the pathway of CHAF1A/ZEB1 was upregulated. In summary, our research indicated that the miR-1179 might regulate CHAF1A/ZEB1 axis and inhibit the invasion of cervical cancer cells.

摘要

miR-1179 的抗癌作用已在许多肿瘤中得到广泛研究。然而,miR-1179 在宫颈癌中的作用机制在很大程度上仍然未知。在本研究中,miR-1179 在宫颈癌细胞系和癌症组织中均下调。此外,miR-1179 模拟物抑制了宫颈癌 SiHa 和 Caski 细胞的侵袭和上皮-间充质转化(EMT)。我们发现染色质组装因子 1 亚基 A(CHAF1A)可能是 miR-1179 的直接靶标,并受 miR-1179 调节。此外,CHAF1A shRNA 抑制了宫颈癌细胞的侵袭和 EMT 促进蛋白的表达。相反,CHAF1A 的过表达不仅促进了宫颈癌细胞的侵袭,而且上调了 EMT 相关蛋白锌指 E 盒结合蛋白 1(ZEB1)的水平。ZEB1 的诱导可以被 miR-1179 的过表达抵消。在宫颈癌患者的组织中观察到,miR-1179 下调,而 CHAF1A/ZEB1 通路上调。总之,我们的研究表明,miR-1179 可能通过调节 CHAF1A/ZEB1 轴抑制宫颈癌细胞的侵袭。

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