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微小RNA-29c通过靶向丝氨酸蛋白酶抑制剂H1抑制口腔鳞状细胞癌的转移并促进其细胞周期停滞。

MiR-29c inhibits the metastasis of oral squamous cell carcinoma and promotes its cell cycle arrest by targeting SERPINH1.

作者信息

Wang Chuanning, Wang Zhiming, Zhang Liping, Lin Xiaoping

机构信息

Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Ann Transl Med. 2021 Sep;9(18):1423. doi: 10.21037/atm-21-3720.

DOI:10.21037/atm-21-3720
PMID:34733975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8506711/
Abstract

BACKGROUND

A large number of studies have shown that the imbalance of micro RNA (miRNA) and its target genes can promote the development of tumors. The purpose of this study was to investigate the biological role and molecular mechanism of serpin peptidase inhibitor clade H member 1 (SERPINH1) and its upstream regulator miR-29c in oral squamous cell carcinoma (OSCC).

METHODS

The expression levels of SERPINH1 and miR-29c were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. The proliferation, apoptosis, metastasis, and cell cycle were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, would healing assay, transwell assay, flow cytometry, and dual luciferase reporter assay.

RESULTS

High expression of SERPINH1 was detected in patients with OSCC and it can be used as a prognostic biomarker for OSCC. Cell function experiments showed that silencing the expression of SERPINH1 inhibited the proliferation and migration of OSCC cells and caused cell cycle arrest at S phase. Bioinformatics analysis showed that there was a binding site between miR-29c and SERPINH1, indicating that miR-29c may regulate the expression of SERPINH1. In addition, miR-29c overexpression inhibited the proliferation and metastasis of OSCC cells, and the subsequent rescue experiment showed that SERPINH1 overexpression can reverse the inhibitory effect of miR-29c in OSCC cell proliferation, migration, apoptosis, and cell cycle arrest.

CONCLUSIONS

The miRNA, miR-29c can regulate the proliferation, migration, invasion, and cell cycle of OSCC cells by targeting SERPINH1.

摘要

背景

大量研究表明,微小RNA(miRNA)及其靶基因的失衡可促进肿瘤的发展。本研究旨在探讨丝氨酸蛋白酶抑制剂H家族成员1(SERPINH1)及其上游调节因子miR-29c在口腔鳞状细胞癌(OSCC)中的生物学作用及分子机制。

方法

采用定量逆转录聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法检测SERPINH1和miR-29c的表达水平。通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法、伤口愈合实验、Transwell实验、流式细胞术和双荧光素酶报告基因实验检测细胞的增殖、凋亡、迁移和细胞周期。

结果

在OSCC患者中检测到SERPINH1高表达,其可作为OSCC的预后生物标志物。细胞功能实验表明,沉默SERPINH1的表达可抑制OSCC细胞的增殖和迁移,并使细胞周期停滞于S期。生物信息学分析显示,miR-29c与SERPINH1之间存在结合位点,提示miR-29c可能调控SERPINH1的表达。此外,miR-29c过表达抑制了OSCC细胞的增殖和转移,随后的拯救实验表明,SERPINH1过表达可逆转miR-29c对OSCC细胞增殖、迁移、凋亡和细胞周期停滞的抑制作用。

结论

miRNA,即miR-29c可通过靶向SERPINH1调控OSCC细胞的增殖、迁移、侵袭和细胞周期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/abffbc4aa251/atm-09-18-1423-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/5d8b03fed525/atm-09-18-1423-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/13fa28283a37/atm-09-18-1423-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/98ad30f1e063/atm-09-18-1423-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/abffbc4aa251/atm-09-18-1423-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/5d8b03fed525/atm-09-18-1423-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/13fa28283a37/atm-09-18-1423-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/98ad30f1e063/atm-09-18-1423-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e095/8506711/abffbc4aa251/atm-09-18-1423-f4.jpg

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