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miR-34a-5p suppresses the invasion and metastasis of liver cancer by targeting the transcription factor YY1 to mediate MYCT1 upregulation.
Acta Histochemica ( IF 2.5 ) Pub Date : 2020-07-08 , DOI: 10.1016/j.acthis.2020.151576
Xiao-Ping Xu 1 , Xiang-Qun Peng 1 , Xin-Min Yin 1 , Yi Liu 1 , Ze-Ya Shi 2
Affiliation  

Background

In recent years, microRNAs (miRNAs) are reported to act as molecular biomarkers for cancer diagnosis, treatment, and prognosis (including liver cancer) and to be involved in the development and progression of cancer and other physiological and pathological changes. However, the role of miR-34a-5p in liver cancer is still largely unknown.

Methods

In our study, the expression of miR-34a-5p in liver cancer tissues and HCC cell lines was detected by qRT-PCR. The CCK-8, scratch wound-healing motility and Transwell assays were used to evaluate the effect on cell proliferation, migration and invasion. The expression of YY1, E-cadherin, N-cadherin and vimentin was analysed by western blotting. The dual luciferase assay was performed to confirm whether YY1 is a target of miR-34a-5p. The combination of YY1 and MYCT1 was detected by chromatin immunoprecipitation (ChIP) assay.

Results

The results showed that miR-34a-5p was downregulated in liver cancer tissues and HCC cell lines. Overexpression of miR-34a-5p inhibited the proliferation, migration and invasion of liver cancer cells. YY1 was a direct target of miR-34a-5p, and the expression of YY1 could reverse the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells. YY1 inhibited MYCT1 expression by directly binding to its promoter region, and knockdown of MYCT1 reversed the influence of miR-34a-5p on the proliferation, migration and invasion of liver cancer cells.

Conclusion

Our results suggest that miR-34a-5p could inhibit the invasion and metastasis of hepatoma cells by targeting YY1-mediated MYCT1 transcriptional repression.



中文翻译:

miR-34a-5p通过靶向转录因子YY1介导MYCT1上调来抑制肝癌的侵袭和转移。

背景

近年来,据报道,微小RNA(miRNA)充当癌症诊断,治疗和预后(包括肝癌)的分子生物标记,并参与癌症的发展和进程以及其他生理和病理变化。但是,miR-34a-5p在肝癌中的作用仍然未知。

方法

在我们的研究中,通过qRT-PCR检测到miR-34a-5p在肝癌组织和HCC细胞系中的表达。使用CCK-8,从头开始的伤口愈合运动性和Transwell测定来评估对细胞增殖,迁移和侵袭的影响。用western blotting分析YY1,E-cadherin,N-cadherin和波形蛋白的表达。进行双重荧光素酶测定以确认YY1是否是miR-34a-5p的靶标。YY1和MYCT1的组合通过染色质免疫沉淀(ChIP)分析进行检测。

结果

结果表明,miR-34a-5p在肝癌组织和HCC细胞系中被下调。miR-34a-5p的过表达抑制肝癌细胞的增殖,迁移和侵袭。YY1是miR-34a-5p的直接靶标,YY1的表达可以逆转miR-34a-5p对肝癌细胞增殖,迁移和侵袭的影响。YY1通过直接与其启动子区结合来抑制MYCT1的表达,而敲低MYCT1则逆转了miR-34a-5p对肝癌细胞增殖,迁移和侵袭的影响。

结论

我们的结果表明,miR-34a-5p可以通过靶向YY1介导的MYCT1转录抑制来抑制肝癌细胞的侵袭和转移。

更新日期:2020-07-08
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