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整合素亚单位α 5（ITGA5）基因环状 RNA 在结直肠癌细胞和组织中吸附 microRNA-107 并调节叉头框 J3（FOXJ3）基因的表达。

Integrin Subunit Alpha 5 (ITGA5) Gene Circular RNA Sponges microRNA-107 in Colorectal Carcinoma Cells and Tissues and Regulates the Expression of the Forkhead Box J3 (FOXJ3) Gene.

机构信息

Department of General Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China (mainland).

Department of General Surgery, Zhejiang Provincial Peoples' Hospital, Peoples' Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2020 Apr 19;26:e920623. doi: 10.12659/MSM.920623.

DOI:10.12659/MSM.920623
PMID:32305992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7191964/
Abstract

BACKGROUND Circular RNAs (circRNAs) can function as sponges for microRNA (miRNA) in carcinogenesis. This study aimed to investigate the role of the circRNA of the integrin subunit alpha 5 (ITGA5) gene and microRNA-107 (miR-107) in human colorectal carcinoma (CRC) cells in vitro and tissue samples from patients with CRC and the expression of forkhead box J3 (FOXJ3) protein. MATERIAL AND METHODS Thirty paired CRC tissue samples and adjacent normal colon tissue samples were studied. Human CRC cell lines, including HT29, SW480, LoVo, and HIEC cells, were studied for cell proliferation using the cell counting kit-8 (CCK-8) assay. Cell migration was studied using a transwell assay, and cell apoptosis was determined using flow cytometry. The luciferase reporter assay was used to study the interactions between ITGA5 circRNA, FOXJ3, and miR-107 in human CRC cells. The expression of ITGA5 circRNA and miR-107 was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of FOXJ3 were measured by Western blot. RESULTS The expression of ITGA5 circRNA was significantly reduced in CRC tissues and CRC cell lines. High ITGA5 circRNA expression inhibited the proliferation and cell migration of CRC cells and promoted the apoptosis of CRC cells. The luciferase reporter assay confirmed that ITGA5 circRNA bound to miR-107, which directly targeted FOXJ3. CONCLUSIONS ITGA5 circRNA may act as a sponge for miR-107 to upregulate FOXJ3 expression and act as a tumor suppressor in CRC cells.

摘要

背景

环状 RNA（circRNAs）可以在致癌作用中作为 microRNA（miRNA）的海绵。本研究旨在探讨整合素亚单位 alpha 5（ITGA5）基因的 circRNA 和 microRNA-107（miR-107）在体外人结直肠癌（CRC）细胞以及 CRC 患者组织样本中叉头框 J3（FOXJ3）蛋白表达中的作用。

材料和方法

研究了 30 对 CRC 组织样本和相邻正常结肠组织样本。使用细胞计数试剂盒-8（CCK-8）测定法研究了包括 HT29、SW480、LoVo 和 HIEC 细胞在内的人 CRC 细胞系的细胞增殖。使用 Transwell 测定法研究细胞迁移，使用流式细胞术测定细胞凋亡。使用荧光素酶报告基因测定法研究 ITGA5 circRNA、FOXJ3 和 miR-107 之间在人 CRC 细胞中的相互作用。使用定量实时聚合酶链反应（qRT-PCR）测定 ITGA5 circRNA 和 miR-107 的表达。通过 Western blot 测定 FOXJ3 的蛋白水平。

结果

CRC 组织和 CRC 细胞系中 ITGA5 circRNA 的表达明显降低。高 ITGA5 circRNA 表达抑制 CRC 细胞的增殖和细胞迁移，并促进 CRC 细胞的凋亡。荧光素酶报告基因测定证实 ITGA5 circRNA 与 miR-107 结合，后者直接靶向 FOXJ3。

结论

ITGA5 circRNA 可能作为 miR-107 的海绵，上调 FOXJ3 表达，并在 CRC 细胞中作为肿瘤抑制因子发挥作用。

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