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微小RNA-17-5p通过调控热休克蛋白B2促进结直肠癌的侵袭和迁移。

miR-17-5p promotes the invasion and migration of colorectal cancer by regulating HSPB2.

作者信息

Yu Weifang, Wang Jia, Li Chao, Xuan Mingda, Han Shuangshuang, Zhang Yingfu, Liu Pengfei, Zhao Zengren

机构信息

Departments of Endoscopy Center, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, 050031 Hebei, China.

Department of Internal medicine, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, 050031 Hebei, China.

出版信息

J Cancer. 2022 Jan 1;13(3):918-931. doi: 10.7150/jca.65614. eCollection 2022.

Abstract

MicroRNA (miRNA) can affect tumor progression by regulating cell proliferation, apoptosis and metastasis. A significant upregulation of miR-17-5p expression was found in colorectal cancer (CRC) tissues by miRNA microarray chip analysis. However, the underlying mechanism of miR-17-5p in CRC is still unclear. The mRNA expression of miR-17-5p was significantly higher in CRC tissues than in adjacent normal tissues. In CRC group, the expression of miR-17-5p in cancer tissues with lymph node metastasis was higher compared with those without lymph node metastasis. The biological function of miR-17-5p was demonstrated through CCK-8, colony formation, flow cytometry and transwell assays. Overexpression of miR-17-5p inhibited CRC cell apoptosis, as well as promoting proliferation, migration and invasion. Transcriptome sequencing and miRNA target prediction software suggested that HSPB2 might be a target gene of miR-17-5p and luciferase reporter detection validated for the first time that miR-17-5p binds directly to the 3'-UTR of HSPB2. In the rescue experiment, the tumor suppressive effect of HSPB2 was detected and miR-17-5p could promote cell proliferation, migration and invasion by targeting HSPB2. Taken together, miR-17-5p promotes invasion and migration by inhibiting HSPB2 in CRC, thereby implicating its potential as a novel diagnostic biomarker and therapeutic target for CRC.

摘要

微小RNA(miRNA)可通过调节细胞增殖、凋亡和转移来影响肿瘤进展。通过miRNA微阵列芯片分析发现,结直肠癌(CRC)组织中miR-17-5p表达显著上调。然而,miR-17-5p在CRC中的潜在机制仍不清楚。CRC组织中miR-17-5p的mRNA表达明显高于相邻正常组织。在CRC组中,有淋巴结转移的癌组织中miR-17-5p的表达高于无淋巴结转移的组织。通过CCK-8、集落形成、流式细胞术和Transwell实验证实了miR-17-5p的生物学功能。miR-17-5p的过表达抑制了CRC细胞凋亡,同时促进了细胞增殖、迁移和侵袭。转录组测序和miRNA靶标预测软件表明,HSPB2可能是miR-17-5p的靶基因,荧光素酶报告基因检测首次验证了miR-17-5p直接与HSPB2的3'-UTR结合。在挽救实验中,检测到HSPB2的抑癌作用,miR-17-5p可通过靶向HSPB2促进细胞增殖、迁移和侵袭。综上所述,miR-17-5p通过抑制CRC中的HSPB2促进侵袭和迁移,从而暗示其作为CRC新型诊断生物标志物和治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a059/8824900/b9de6255e968/jcav13p0918g001.jpg

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