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撤稿文章:MiR-182-5p和miR-96-5p通过靶向RND3部分增加了肝癌细胞的迁移、增殖和顺铂耐药性。

Retracted Article: MiR-182-5p and miR-96-5p increased hepatocellular carcinoma cell mobility, proliferation and cisplatin resistance partially by targeting RND3.

作者信息

Yang Shiming, Chen Zhi, Fan Daguang, Zhang Rui, Zhang Yuhong, Wu Shusheng

机构信息

Department of General Surgery, Shanxi Provincial People's Hospital No. 29, Shuangtaisi Street Taiyuan Shanxi 030012 China

出版信息

RSC Adv. 2018 Oct 12;8(61):34973-34983. doi: 10.1039/c8ra07055e. eCollection 2018 Oct 10.

Abstract

We investigated whether miR-182-5p or miR-96-5p could increase hepatocellular carcinoma (HCC) development by targeting Rho Family GTPase 3 (RND3) gene expression. The expression levels of miR-182-5p, miR-96-5p and mRNA/protein of RND3 in non-HCC liver tissue, HCC tissue and adjacent tissue specimens were evaluated by RT-qPCR and western blot. Patient-derived HCC cell culture was established, and miR-182-5p or miR-96-5p agomir or antagomir treatment was performed to mimic the overexpression or knockdown of the two miRNAs. HCC cell mobility was monitored by trans-well migration and invasion assay, while HCC cell growth was evaluated by cell viability, proliferation and apoptosis assay. HCC cell apoptosis was further investigated by caspase-3/-8/-9 activity assay. MiR-182-5p and miR-96-5p were significantly upregulated in HCC tissue specimens compared with non-HCC or adjacent tissue specimens, inversely correlating to RND3 mRNA expression level. Treatment with miR-182-5p or miR-96-5p agomir significantly reduced RND3 mRNA/protein expression level in HCC cells. MiR-182-5p- or miR-96-5p-targeting RND3 mRNA was verified by luciferase reporter assay and AGO2-RNA immunoprecipitation assay. MiR-182-5p or miR-96-5p agomir treatment significantly rescued HCC cell migration and invasion that were repressed by RND3 overexpression, during which ROCK1 and ROCK2 inhibition were involved. MiR-182-5p or miR-96-5p agomir treatment also increased HCC cell proliferation and cisplatin resistance , which could be antagonized by RND3 overexpression or ROCK inhibition. Thus, miR-182-5p and miR-96-5p increased HCC cell mobility, proliferation and cisplatin resistance partially by targeting RND3.

摘要

我们研究了miR-182-5p或miR-96-5p是否通过靶向Rho家族GTP酶3(RND3)基因表达来促进肝细胞癌(HCC)的发展。通过RT-qPCR和蛋白质印迹法评估非HCC肝组织、HCC组织及相邻组织标本中miR-182-5p、miR-96-5p以及RND3的mRNA/蛋白质表达水平。建立患者来源的HCC细胞培养体系,进行miR-182-5p或miR-96-5p激动剂或拮抗剂处理,以模拟这两种微小RNA的过表达或敲低。通过Transwell迁移和侵袭实验监测HCC细胞迁移能力,通过细胞活力、增殖和凋亡实验评估HCC细胞生长情况。通过caspase-3/-8/-9活性实验进一步研究HCC细胞凋亡情况。与非HCC或相邻组织标本相比,HCC组织标本中miR-182-5p和miR-96-5p显著上调,与RND3 mRNA表达水平呈负相关。用miR-182-5p或miR-96-5p激动剂处理可显著降低HCC细胞中RND3 mRNA/蛋白质表达水平通过荧光素酶报告基因实验和AGO2-RNA免疫沉淀实验验证了miR-182-5p或miR-96-5p靶向RND3 mRNA。miR-182-5p或miR-96-5p激动剂处理显著挽救了被RND3过表达抑制的HCC细胞迁移和侵袭能力,其中涉及ROCK1和ROCK2的抑制。miR-182-5p或miR-96-5p激动剂处理还增加了HCC细胞增殖和顺铂耐药性,而RND3过表达或ROCK抑制可拮抗这种作用。因此,miR-182-5p和miR-96-5p部分通过靶向RND3增加了HCC细胞迁移、增殖和顺铂耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a605/9087357/fcb06dfc4d01/c8ra07055e-f1.jpg

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