HOXA11-AS promotes the progression of oral squamous cell carcinoma by targeting the miR-518a-3p/PDK1 axis

Cancer Cell International

Susheng Miao¹  Baojun Li¹  Cheng Xiang²  Rong Pei²  Guofu Li²  Yuanjing Lv²  Wei Wang³ 

[1] 0000 0001 2204 9268, grid.410736.7, Department of Head and Neck Surgery, The Affiliated Tumour Hospital, Harbin Medical University, 150081, Harbin, Heilongjiang, People’s Republic of China;0000 0001 2204 9268, grid.410736.7, Department of Neurosurgery, The Affiliated Tumour Hospital, Harbin Medical University, No. 150 Haping Road, Nangang District, 150081, Harbin, Heilongjiang, People’s Republic of China;0000 0001 2204 9268, grid.410736.7, Department of Oral Maxillofacial Surgery, The First Affiliated Hospital, Harbin Medical University, 150001, Harbin, Heilongjiang, People’s Republic of China;

关键词: Oral squamous cell carcinoma;    HOXA11-AS;    miR-518a-3p;    PDK1;   

DOI  :  10.1186/s12935-019-0838-6

来源: publisher

【 摘 要 】

BackgroundLong non-coding RNAs (lncRNAs) are promising therapeutic molecules of cancer. Here we aim to study the therapeutic effect and mechanism of a lncRNA, HOXA11-AS, in oral squamous cell carcinoma (OSCC).MethodsOSCC tissues and adjacent matched paraneoplastic normal tissues used in this study were collected from 42 OSCC patients. The significant downregulation or upregulation of HOXA11-AS expression in OSCC cells was confirmed by quantitative real-time PCR (qRT-PCR). Bioinformatics analysis of StarBase were performed to investigate the potential microRNAs mediated by HOXA11-AS. HOXA11-AS-transfected cells or control cells were subcutaneously injected into nude mice to further determine the effects of HOXA11-AS on OSCC progression in vivo.ResultsqRT-PCR analysis indicated that HOXA11-AS expression was significantly upregulated in OSCC tissues. Functional studies revealed that HOXA11-AS significantly promotes cell proliferation, reduces the percentage of G0/G1 phase cells and enhances the cell invasion in OSCC. Bioinformatics analysis suggested that a microRNA (miRNA), miR-518a-3p, is as a target of HOXA11-AS. Alteration of miR-518a-3p levels by HOXA11-AS transduced to changes in PDK1 expression. In a mouse model of OSCC, HOXA11-AS overexpression promoted tumor growth, concomitant with reduced miR-518a-3p expression and increased PDK1 expression.ConclusionTaken together, our study demonstrates that HOXA11-AS/miR-518a-3p/PDK1 axis is an important regulator of OSCC progression and may serve as a potential therapeutic target in OSCC. HARMU20150128, registered at Jan, 28 2018.

【 授权许可】

CC BY