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长链非编码 RNA 癌症易感性候选物 7 的抑制作用通过靶向 microRNA-30a-5p 来减弱肝癌的发展。

Inhibition of long noncoding RNA cancer susceptibility candidate 7 attenuates hepatocellular carcinoma development by targeting microRNA-30a-5p.

机构信息

Hepatobiliary Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.

出版信息

Bioengineered. 2022 Apr;13(4):11296-11308. doi: 10.1080/21655979.2022.2068289.

Abstract

Long non-coding RNA (lncRNA) cancer susceptibility candidate 7 (CASC7) was reported to be participated in tumor development. This study was carried out to investigate the functions of CASC7 in hepatocellular carcinoma (HCC) progression. The expression of CASC7 and microRNA-30a-5p (miR-30a-5p) in HCC tissues and cells were detected by quantitative Real-time PCR (qRT-PCR). The expression of Krueppel-like factor 10 (KLF10), transforming growth factor-β (TGF-β), and SMAD3 were detected by Western Blot analysis. Transwell assay, flow cytometry, Cell Counting Kit-8 (CCK-8) assay and colony formation assay were performed to evaluate the effects of CASC7, KLF10 and miR-30a-5p on cell function. The relationship among CASC7, KLF10 and miR-30a-5p was evaluated by luciferase reporter assay and bioinformatics analyses. Tumor growth was detected in nude mice. The expression levels of CASC7 were increased and the expression levels of miR-30a-5p were reduced in HCC cells and tissues. Knockdown of CASC7 and overexpression of miR-30a-5p reduced tumor growth as well as HCC cell proliferation, invasion and migration. In HCC tumor tissues, the expression of miR-30a-5p was negatively correlated with the expression of CASC7. Moreover, as a target of miR-30a-5p, KLF10 was regulated by CASC7 and miR-30a-5p, and CASC7 regulated the KLF10/TGF-β/SMAD3 pathway via binding to miR-30a-5p, thereby promoting HCC cell progression.

摘要

长链非编码 RNA(lncRNA)癌症易感性候选物 7(CASC7)被报道参与肿瘤的发生。本研究旨在探讨 CASC7 在肝细胞癌(HCC)进展中的作用。采用实时定量 PCR(qRT-PCR)检测 HCC 组织和细胞中 CASC7 和 microRNA-30a-5p(miR-30a-5p)的表达。采用 Western blot 分析检测 Krueppel 样因子 10(KLF10)、转化生长因子-β(TGF-β)和 SMAD3 的表达。通过 Transwell 试验、流式细胞术、细胞计数试剂盒-8(CCK-8)试验和集落形成试验评估 CASC7、KLF10 和 miR-30a-5p 对细胞功能的影响。通过荧光素酶报告基因检测和生物信息学分析评估 CASC7、KLF10 和 miR-30a-5p 之间的关系。在裸鼠中检测肿瘤生长。CASC7 在 HCC 细胞和组织中的表达水平升高,miR-30a-5p 的表达水平降低。敲低 CASC7 和过表达 miR-30a-5p 均降低肿瘤生长和 HCC 细胞增殖、侵袭和迁移。在 HCC 肿瘤组织中,miR-30a-5p 的表达与 CASC7 的表达呈负相关。此外,作为 miR-30a-5p 的靶基因,KLF10 受 CASC7 和 miR-30a-5p 的调控,CASC7 通过与 miR-30a-5p 结合调节 KLF10/TGF-β/SMAD3 通路,从而促进 HCC 细胞的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56d8/9208517/0ed846d919db/KBIE_A_2068289_UF0001_OC.jpg

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