Circ-SNX27海绵miR-375/RPN1轴有助于肝细胞癌的进展。

IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Korean Journal of Physiology & Pharmacology Pub Date : 2023-07-01 DOI:10.4196/kjpp.2023.27.4.333
Chao Zheng, Jin Liang, Shoude Yu, Hua Xu, Lin Dai, Dan Xu
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引用次数: 0

摘要

肝细胞癌(HCC)是一种常见的恶性肿瘤,病死率高。circ-SNX27是否能影响HCC的进展尚未有报道。本研究试图分析circ-SNX27在HCC中的确切作用和潜在机制。采用实时荧光定量PCR和Western blotting对肝癌细胞系和肝癌患者肿瘤标本进行分析,定量circ-SNX27、miR-375和核糖蛋白I (RPN1)的表达。细胞侵袭及细胞计数试剂盒8实验评价HCC细胞侵袭及增殖情况。Caspase-3活性测定试剂盒检测Caspase-3活性。荧光素酶报告基因和RNA免疫沉淀测定确定miR-375、circ-SNX27和RPN1之间的关系。为了确定circ-SNX27敲低如何影响体内肝癌异种移植物的生长,我们构建了荷瘤小鼠模型。在HCC细胞和HCC患者肿瘤标本中观察到circ-SNX27和RPN1表达升高,miR-375表达降低。在HCC细胞中敲低circ-SNX27会降低其增殖和侵袭能力,但会提高其caspase-3活性。此外,低水平的circ-SNX27抑制了小鼠HCC肿瘤的生长。Circ-SNX27通过与miR-375竞争性结合增强RPN1。在HCC细胞中沉默miR-375可促进其恶性表型。尽管如此,miR-375沉默的促进作用通过敲低circ-SNX27或RPN1是可逆的。本研究表明circ-SNX27通过调节miR-375/RPN1轴加速HCC的进展。这表明circ-SNX27作为HCC治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Circ-SNX27 sponging miR-375/RPN1 axis contributes to hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high fatality. It has yet to be reported whether circ-SNX27 can affect the progression of HCC. This study attempted to analyze circ-SNX27's precise role and underlying mechanisms in HCC. HCC cell lines and tumor specimens from HCC patients were analyzed using quantitative real-time PCR and Western blotting to quantify the expressions of circ-SNX27, miR-375, and ribophorin I (RPN1). Cell invasion and cell counting kit 8 experiments were conducted for the evaluation of HCC cell invasion and proliferation. Caspase-3 Activity Assay Kit was utilized to gauge the caspase-3 activity. Luciferase reporter and RNA immunoprecipitation assays were executed to ascertain the relationships among miR-375, circ-SNX27, and RPN1. To determine how circ-SNX27 knockdown affects the growth of HCC xenografts in vivo, tumor-bearing mouse models were constructed. Elevated expressions of circ-SNX27 and RPN1 as well as a reduced miR-375 expression were observed among HCC cells and HCC patient tumor specimens. Knocking-down circ-SNX27 in HCC cells abated their proliferative and invasive abilities but raised their caspase-3 activity. Moreover, the poor levels of circ-SNX27 inhibited HCC tumor growth among the mice. Circ-SNX27 enhanced RPN1 by competitively binding with miR-375. Silencing miR-375 in HCC cells promoted their malignant phenotypes. Nonetheless, the promotive effect of miR-375 silencing was reversible via the knockdown of circ-SNX27 or RPN1. This research demonstrated that circ-SNX27 accelerated the progression of HCC by modulating the miR-375/RPN1 axis. This is indicative of circ-SNX27's potential as a target for the treatment of HCC.

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来源期刊
Korean Journal of Physiology & Pharmacology
Korean Journal of Physiology & Pharmacology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
CiteScore
3.20
自引率
5.00%
发文量
53
审稿时长
6-12 weeks
期刊介绍: The Korean Journal of Physiology & Pharmacology (Korean J. Physiol. Pharmacol., KJPP) is the official journal of both the Korean Physiological Society (KPS) and the Korean Society of Pharmacology (KSP). The journal launched in 1997 and is published bi-monthly in English. KJPP publishes original, peer-reviewed, scientific research-based articles that report successful advances in physiology and pharmacology. KJPP welcomes the submission of all original research articles in the field of physiology and pharmacology, especially the new and innovative findings. The scope of researches includes the action mechanism, pharmacological effect, utilization, and interaction of chemicals with biological system as well as the development of new drug targets. Theoretical articles that use computational models for further understanding of the physiological or pharmacological processes are also welcomed. Investigative translational research articles on human disease with an emphasis on physiology or pharmacology are also invited. KJPP does not publish work on the actions of crude biological extracts of either unknown chemical composition (e.g. unpurified and unvalidated) or unknown concentration. Reviews are normally commissioned, but consideration will be given to unsolicited contributions. All papers accepted for publication in KJPP will appear simultaneously in the printed Journal and online.
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