Abstract
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.
Highlights
Long non-coding RNAs are promising therapeutic molecules of cancer
HOXA11‐AS was upregulated in oral squamous cell carcinoma (OSCC) tissues and cell lines To investigate the clinical significance of HOXA11-AS in OSCC, total RNA was first extracted from 42 human OSCC tissues and matched paraneoplastic tissues for quantitative real-time PCR (qRT-PCR) analysis
It was shown that HOXA11-AS levels were correlated with grade, clinical stage and lymph node metastasis of OSCC, while HOXA11-AS levels were not correlated to other clinical characteristics, such as gender, age and position in OSCC (Table 2)
Summary
Long non-coding RNAs (lncRNAs) are promising therapeutic molecules of cancer. We aim to study the therapeutic effect and mechanism of a lncRNA, HOXA11-AS, in oral squamous cell carcinoma (OSCC). Oral squamous cell carcinoma (OSCC) is a devastating cancer causing 145,000 deaths worldwide as a result, which accounts to 2.1% of the deaths caused by all cancers. It is estimated that there have been over 300,000 new cases in the recent years [1]. In spite of advances in treatment approaches for oral cancer, there. Long non-coding RNAs (lncRNAs) have gained increasing attention as a new class of regulatory molecules since the completion of the human genome sequencing [6]. A large number of lnRNAs have been associated with cancers. The lncRNA HOTAIR has been shown to have a strong association
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