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miR-105-3p 通过靶向 GOLIM4 作为癌基因促进乳腺癌细胞的增殖和转移。

MiR-105-3p acts as an oncogene to promote the proliferation and metastasis of breast cancer cells by targeting GOLIM4.

机构信息

Department of Pathology, Huai'an Key Laboratory of Gastric Cancer, Jiangsu College of Nursing, No. 9 Keji Road, Huai'an, Jiangsu, 223001, P.R. China.

Office of Educational Administration, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, Jiangxi, China.

出版信息

BMC Cancer. 2021 Mar 15;21(1):275. doi: 10.1186/s12885-021-07909-2.

Abstract

BACKGROUND

Dysregulated miRNAs are involved in carcinogenesis of the breast and may be used as prognostic biomarkers and therapeutic targets during the cancer process. The purpose of this study was to explore the effect of miR-105-3p on the tumourigenicity of breast cancer and its underlying molecular mechanisms.

METHODS

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was applied to detect the expression of miR-105-3p in breast cancer tissues and cell lines. The impacts of miR-105-3p on the proliferation, migration, invasion and apoptosis of human breast cancer cells (MCF-7 and ZR-75-30) were evaluated by CCK-8 assays, Transwell chamber assays, TUNEL assays and western blot analyses. In addition, bioinformatics and luciferase reporter assays were used to determine the target genes of miR-105-3p.

RESULTS

The expression of miR-105-3p was elevated in breast cancer tissues and increased with tumour severity. Downregulation of miR-105-3p could inhibit cell proliferation, suppress cell migration/invasion, and promote cell apoptosis in MCF-7 and ZR-75-30 cells. Furthermore, Golgi integral membrane protein 4 (GOLIM4) was identified as the direct target gene of miR-105-3p by bioinformatics and luciferase reporter assays. In addition, silencing GOLIM4 restored the anti-breast cancer effects induced by miR-105-3p downregulation.

CONCLUSIONS

MiR-105-3p acts as an oncogene to promote the proliferation and metastasis of breast cancer cells by targeting GOLIM4, which provides a new target for the prevention and treatment of breast cancer.

摘要

背景

失调的 miRNAs 参与乳腺癌的发生,可作为癌症过程中的预后生物标志物和治疗靶点。本研究旨在探讨 miR-105-3p 对乳腺癌肿瘤发生的影响及其潜在的分子机制。

方法

采用逆转录定量聚合酶链反应(RT-qPCR)检测乳腺癌组织和细胞系中 miR-105-3p 的表达。通过 CCK-8 检测、Transwell 室检测、TUNEL 检测和 Western blot 分析评估 miR-105-3p 对人乳腺癌细胞(MCF-7 和 ZR-75-30)增殖、迁移、侵袭和凋亡的影响。此外,还采用生物信息学和荧光素酶报告基因检测来确定 miR-105-3p 的靶基因。

结果

miR-105-3p 在乳腺癌组织中的表达升高,并随肿瘤严重程度增加而增加。下调 miR-105-3p 可抑制 MCF-7 和 ZR-75-30 细胞的增殖,抑制细胞迁移/侵袭,并促进细胞凋亡。此外,生物信息学和荧光素酶报告基因检测表明,高尔基整合膜蛋白 4(GOLIM4)是 miR-105-3p 的直接靶基因。此外,沉默 GOLIM4 可恢复 miR-105-3p 下调诱导的抗乳腺癌作用。

结论

miR-105-3p 通过靶向 GOLIM4 发挥癌基因作用,促进乳腺癌细胞的增殖和转移,为乳腺癌的防治提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f4a/7962220/f8582b8865ef/12885_2021_7909_Fig1_HTML.jpg

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