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微小 RNA-299-5p 通过直接靶向丝氨酸/苏氨酸激酶 39 抑制乳腺癌细胞转移。

MicroRNA‑299‑5p inhibits cell metastasis in breast cancer by directly targeting serine/threonine kinase 39.

机构信息

Department of Genetics and Cell Biology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.

Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Preventive Dentistry, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

出版信息

Oncol Rep. 2020 Apr;43(4):1221-1233. doi: 10.3892/or.2020.7486. Epub 2020 Jan 31.

DOI:10.3892/or.2020.7486
PMID:32020227
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7057922/
Abstract

Numerous studies have demonstrated that microRNAs (miRNAs) play a key role in human carcinogenesis and metastasis. For example, miR‑299‑5p has previously been revealed to be dysregulated in several human cancers. However, the biological function of miR‑299‑5p in breast cancer remains unclear. The present study demonstrated that miR‑299‑5p was downregulated in breast cancer tissues and cell lines. The restoration of miR‑299‑5p expression suppressed cell migration and invasion, whereas inhibition of miR‑299‑5p promoted cell migration and invasion. In addition, in vivo studies demonstrated that miR‑299‑5p overexpression was able to inhibit tumour metastasis in nude mice. Mechanistically, through bioinformatics analysis and a dual‑luciferase assay, it was confirmed that miR‑299‑5p directly targets serine/threonine kinase 39 (STK39). Silencing STK39 inhibited cell metastasis and suppressed epithelial‑mesenchymal transition markers and matrix metalloproteinase expression, whereas restoration of STK39 expression was able to reverse miR‑299‑5p‑inhibited cell migration and invasion. Collectively, the results of the present study demonstrated that miR‑299‑5p supresses breast cancer cell migration and invasion by targeting STK39. These findings may provide novel insights into miR‑299‑5p and its potential diagnostic and therapeutic benefits in breast cancer.

摘要

大量研究表明 microRNAs（miRNAs）在人类癌症发生和转移中发挥着关键作用。例如，miR-299-5p 先前已被证实在几种人类癌症中失调。然而，miR-299-5p 在乳腺癌中的生物学功能仍不清楚。本研究表明 miR-299-5p 在乳腺癌组织和细胞系中表达下调。miR-299-5p 表达的恢复抑制了细胞迁移和侵袭，而抑制 miR-299-5p 则促进了细胞迁移和侵袭。此外，体内研究表明 miR-299-5p 的过表达能够抑制裸鼠肿瘤的转移。在机制上，通过生物信息学分析和双荧光素酶报告基因实验证实，miR-299-5p 可直接靶向丝氨酸/苏氨酸激酶 39（STK39）。沉默 STK39 抑制细胞转移，并抑制上皮-间充质转化标志物和基质金属蛋白酶的表达，而恢复 STK39 的表达能够逆转 miR-299-5p 抑制的细胞迁移和侵袭。综上所述，本研究结果表明 miR-299-5p 通过靶向 STK39 抑制乳腺癌细胞的迁移和侵袭。这些发现可能为 miR-299-5p 及其在乳腺癌中的潜在诊断和治疗益处提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/e7bfa3b561d6/OR-43-04-1221-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/f526711b1e37/OR-43-04-1221-g00.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/b33976177518/OR-43-04-1221-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/e7bfa3b561d6/OR-43-04-1221-g07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/f526711b1e37/OR-43-04-1221-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/7c238c0e2515/OR-43-04-1221-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/c958c8830369/OR-43-04-1221-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/54094819ef69/OR-43-04-1221-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/0430b7a855b0/OR-43-04-1221-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/7390a79f2995/OR-43-04-1221-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/b33976177518/OR-43-04-1221-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fef6/7057922/e7bfa3b561d6/OR-43-04-1221-g07.jpg

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