微小RNA-381通过靶向STC2介导头颈部鳞状细胞癌的发展。

miR-381 Mediates the Development of Head and Neck Squamous Cell Carcinoma via Targeting STC2.

作者信息

Ma Hai-Feng, Lv Guo-Xiao, Zhang Da-Hai

机构信息

Department of Radiotherapy, Zhejiang Dongyang People's Hospital, Dongyang 322100, Zhejiang Province, People's Republic of China.

出版信息

Onco Targets Ther. 2020 May 21;13:4485-4493. doi: 10.2147/OTT.S246289. eCollection 2020.

Abstract

OBJECTIVE

miR-381 is implicated in the occurrence and development of various cancers, yet its role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. This study sought to research the direct target of miR-381 in HNSCC and investigate their roles in cancer progression.

METHODS

miRNA and mRNA expression files of HNSCC were accessed from TCGA database and then processed for differential analysis. Bioinformatics databases were employed to predict the target mRNAs of the potential miRNA. qRT-PCR was conducted to determine the expression levels of the target miRNA and mRNA. Then, a series of in vitro experiments like CCK-8, colony formation assay, wound healing assay and transwell assay were performed to detect cell proliferation, migration and invasion. Dual-luciferase reporter gene assay was carried out for the further validation of the targeted relationship between the miRNA and mRNA.

RESULTS

miR-381 was observed to be greatly down-regulated in HNSCC cells, and its overexpression could inhibit cell proliferation, migration and invasion. Besides, dual-luciferase reporter gene assay confirmed that STC2 was a direct target of miR-381, and their expression levels were reversely correlated. Moreover, rescue experiments demonstrated that overexpressing STC2 could rescue the inhibitory effect of miR-381 overexpression on cell proliferation, migration and invasion. Also, we verified that miR-381/STC2 exerted its function on HNSCC proliferation by mediating the FAK/PI3K/Akt/mTOR signaling pathway.

CONCLUSION

miR-381 suppresses cell proliferation, migration and invasion in HNSCC through targeting STC2, and participates in HNSCC development probably via the FAK/PI3K/Akt/mTOR signaling pathway.

摘要

目的

miR - 381与多种癌症的发生发展有关,但其在头颈部鳞状细胞癌(HNSCC)中的作用仍 largely unknown。本研究旨在探究miR - 381在HNSCC中的直接靶点,并研究它们在癌症进展中的作用。

方法

从TCGA数据库获取HNSCC的miRNA和mRNA表达文件,然后进行差异分析。利用生物信息学数据库预测潜在miRNA的靶mRNA。进行qRT - PCR以确定靶miRNA和mRNA的表达水平。然后,进行一系列体外实验,如CCK - 8、集落形成实验、伤口愈合实验和transwell实验,以检测细胞增殖、迁移和侵袭。进行双荧光素酶报告基因实验以进一步验证miRNA与mRNA之间的靶向关系。

结果

观察到miR - 381在HNSCC细胞中显著下调,其过表达可抑制细胞增殖、迁移和侵袭。此外,双荧光素酶报告基因实验证实STC2是miR - 381的直接靶点,且它们的表达水平呈负相关。此外,挽救实验表明过表达STC2可挽救miR - 381过表达对细胞增殖、迁移和侵袭的抑制作用。我们还证实miR - 381/STC2通过介导FAK/PI3K/Akt/mTOR信号通路对HNSCC增殖发挥作用。

结论

miR - 381通过靶向STC2抑制HNSCC细胞的增殖、迁移和侵袭,并可能通过FAK/PI3K/Akt/mTOR信号通路参与HNSCC的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cf9/7247612/b72daeea93ed/OTT-13-4485-g0001.jpg

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