HOXD-AS1 facilitates cell migration and invasion as an oncogenic lncRNA by competitively binding to miR-877-3p and upregulating FGF2 in human cervical cancer

Shaozheng Chen,Kejun Li

doi:10.1186/s12885-020-07441-9

Abstract

BackgroundLong non-coding RNAs (LncRNAs) are dysregulated in multiple human cancers and they are highly involved in tumor progression. Previous studies have identified the oncogenic lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in human cancers, while its roles in cervical cancer (CC) remain unclear. Herein we intended to characterize the implication of HOXD-AS1 in CC.MethodsqRT-PCR was applied to examine the relative expression of HOXD-AS1 in CC tissues, cell lines and transfected cells. Wound healing and transwell assays were applied to detect cell migration and invasion alteration. The targeting relationship between miRNA and mRNA/lncRNA was determined by dual luciferase reporter, qRT-PCR and western blot assays.ResultsHOXD-AS1 was overexpressed in CC tissues and cell lines. Its higher level predicted worse prognosis of CC patients. SiRNA mediated knockdown of HOXD-AS1 repressed CC cell migration and invasion, and its overexpression did the opposite. Mechanistically, HOXD-AS1 acted as a competing endogenous RNA (ceRNA) to sponge miR-877-3p and led to upregulation of FGF2, a target of miR-877-3p. Importantly, either miR-877-3p overexpression or FGF2 inhibition could abolish the migration and invasion promotion induced by HOXD-AS1.ConclusionHOXD-AS1 functions as a tumor-promoting lncRNA via the miR-877-3p/FGF2 axis in CC. HOXD-AS1 might be a promising therapeutic target as well as a novel prognostic biomarker for CC.

Highlights

Long non-coding RNAs (LncRNAs) are dysregulated in multiple human cancers and they are highly involved in tumor progression
Increased expression of HOXD-AS1 is correlated with poor prognosis of CC patients We firstly detected the expression of HOXD-AS1 in 40 pairs of CC tissues by qRT-PCR
According to the classification of the clinical stages of these CC patients, we found that HOXD-AS1 expression was higher in advanced CC stages (III + IV vs. I + II; Fig. 1b)

Summary

Introduction

Long non-coding RNAs (LncRNAs) are dysregulated in multiple human cancers and they are highly involved in tumor progression. Previous studies have identified the oncogenic lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in human cancers, while its roles in cervical cancer (CC) remain unclear. Cervical cancer (CC) is a frequent gynecological malignancy leading the highly fatality rate in women [1]. Infection by human papillomavirus (HPV) is a major cause of cervical carcinogenesis [5, 6], but the detailed mechanisms stay unclear. The 5-year survival rate of CC at the early stages is over 85%, whereas the survival of most CC patients at the advanced stages is unsatisfactory (lower than 40%) [7,8,9]. It is urgent to investigate the internal mechanisms of CC progression to develop novel anticancer strategies

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Discussion

Conclusion