Overexpression of long noncoding RNA HOXB-AS3 indicates an unfavorable prognosis and promotes tumorigenesis in epithelial ovarian cancer via Wnt/β-catenin signaling pathway.

Xiao-Hong Zhuang,Ying Liu,Jin-Ling Li

doi:10.1042/bsr20190906

Xiao-Hong Zhuang, Ying Liu + Show 1 more

Open Access

https://doi.org/10.1042/bsr20190906

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Journal: Bioscience reports	Publication Date: Aug 2, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: Qingdao University, Linyi People's Hospital

Abstract

Long noncoding RNA HOXB cluster antisense RNA 3 (HOXB-AS3) has been reported to be dysregulated in several tumors. The present study mainly aims at the investigation in how HOXB-AS3 works in epithelial ovarian cancer (EOC) and to elucidate the mechanism involved. Initially, ‘GEPIA’ was mined to examine the differential expression levels and prognostic value of HOXB-AS3 in EOC patients. The expression of HOXB-AS3 in EOC cell lines and patient specimens was examined with quantitative RT-PCR. Simultaneously, the correlation of HOXB-AS3 expression with a variety of clinicopathological factors and patient survival was analyzed. MTT, colony formation and flow cytometry assays were performed to analyze the cell viability of EOC cells. Wound healing and Transwell assays were carried out to determine EOC cells’ capability of migrating and invading. The impact of HOXB-AS3 on EMT and Wnt/β-catenin signaling was explored with the approach of Western blot. We found that in both EOC cell lines and tissues, HOXB-AS3 expression was significantly up-regulated, and its high expression was an independent prognostic marker of poor outcome for EOC patients. In vitro loss-of-function assays revealed that HOXB-AS3 knockdown inhibited EOC cells proliferation, migration, invasion and EMT, and induced EOC cells’ apoptosis. Furthermore, we validated that down-regulated HOXB-AS3 attenuated the activity of Wnt/β-catenin signaling to suppress the invasion, migration and proliferation of EOC cells. To sum up, the present study came up with the conclusion that HOXB-AS3 acts as an oncogenic gene in EOC progression through HOXB-AS3-Wnt/β-catenin signaling regulation, providing a novel insight into EOC tumorigenesis.

Highlights

Human ovarian cancer, one of the most common gynecologic neoplasms, is responsible for the highest mortality among women, and represents a major concern for women’s health worldwide [1,2]
Homeobox B cluster (HOXB)-AS3 was overexpressed in epithelial ovarian cancer (EOC) patients and associated with poor clinical outcome
To identify possible Long noncoding RNA (lncRNA) that may be involved in EOC and development, we first analyzed lncRNAs expressing profiles by an online tool ‘Gene Expression Profiling Interactive Analysis (GEPIA)’ which collects clinical data from The cancer genome atlas (TCGA) database [20]

Summary

Introduction

One of the most common gynecologic neoplasms, is responsible for the highest mortality among women, and represents a major concern for women’s health worldwide [1,2]. Nearly nine in ten female ovarian cancer patients are diagnosed with epithelial ovarian cancer (EOC) [3]. Despite the current EOC treatment approaches, such as radiotherapy, chemotherapy and operation, have considerably advanced and improved, the clinical outcome of EOC patients is still very unsatisfactory, which has reflected in a disappointing 5-year survival rate of only 38% among treated EOC patients [4,5,6]. The diagnoses of most EOC patients cannot be confirmed until the disease develops to a late stage, which is a major contributor to the unsatisfactory survival rate. Great efforts need to be made to identify key molecules involved in the pathogenesis of EOC, which could help in EOC’s early detection and improvement of current treatment

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