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SLCO4A1反义RNA1通过miR-4673/驱动蛋白家族成员21B轴介导胰腺癌的发展。

SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis.

作者信息

Zhang Jianxin, Shen Yanbing, Ma Dandan, Li Zhonghu, Zhang Zhiyong, Jin Weidong

机构信息

Department of General Surgery, General Hospital of Central Theater Command, Wuhan 430070, Hubei, China.

Department of General Surgery, General Hospital of Central Theater Command, 627 Wuluo Road, Wuchang District, Wuhan 430070, Hubei, China.

出版信息

Open Med (Wars). 2022 Feb 14;17(1):253-265. doi: 10.1515/med-2022-0418. eCollection 2022.

Abstract

In this study, we intended to figure out the biological significance of long non-coding RNAs (lncRNAs) solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1-AS1) in pancreatic cancer (PC). Cell counting kit-8, colony formation, wound healing, transwell, and flow cytometry experiments were performed to reveal how SLCO4A1-AS1 influences PC cell proliferation, migration, invasion, and apoptosis. Thereafter, bioinformatics analysis, RNA immunoprecipitation assay, luciferase reporter assay, and RNA pull-down assay were applied for determining the binding sites and binding capacities between SLCO4A1-AS1 and miR-4673 or kinesin family member 21B (KIF21B) and miR-4673. The results depicted that SLCO4A1-AS1 was upregulated in PC, and SLCO4A1-AS1 knockdown suppressed PC cell growth, migration, invasion, and induced cell apoptosis. Furthermore, SLCO4A1-AS1 was verified to modulate the expression of KIF21B by binding with miR-4673. SLCO4A1-AS1 exerted an oncogenic function in PC. The overexpression of SLCO4A1-AS1 aggravated the malignant behaviors of PC via the upregulation of KIF21B by sponging miR-4673. Our findings revealed a novel molecular mechanism mediated by SLCO4A1-AS1, which might play a significant role in modulating the biological processes of PC.

摘要

在本研究中,我们旨在探究长链非编码RNA(lncRNA)溶质载体有机阴离子转运体家族成员4A1反义RNA 1(SLCO4A1-AS1)在胰腺癌(PC)中的生物学意义。进行了细胞计数试剂盒-8、集落形成、伤口愈合、Transwell和流式细胞术实验,以揭示SLCO4A1-AS1如何影响PC细胞的增殖、迁移、侵袭和凋亡。此后,应用生物信息学分析、RNA免疫沉淀测定、荧光素酶报告基因测定和RNA下拉测定,以确定SLCO4A1-AS1与miR-4673或驱动蛋白家族成员21B(KIF21B)和miR-4673之间的结合位点和结合能力。结果表明,SLCO4A1-AS1在PC中上调,SLCO4A1-AS1敲低抑制PC细胞生长、迁移、侵袭并诱导细胞凋亡。此外,证实SLCO4A1-AS1通过与miR-4673结合来调节KIF21B的表达。SLCO4A1-AS1在PC中发挥致癌作用。SLCO4A1-AS1的过表达通过海绵化miR-4673上调KIF21B,从而加剧PC的恶性行为。我们的研究结果揭示了一种由SLCO4A1-AS1介导的新分子机制,其可能在调节PC的生物学过程中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4b6/8847713/738d29b6454a/j_med-2022-0418-fig001.jpg

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