LncRNAs expression profiling in normal ovary, benign ovarian cyst and malignant epithelial ovarian cancer.

Huan Wang,Juan Xu,Jingmin Zhang,Ziyi Fu,Genmei Jia,Yun Gu,Mingming Lv,Jian Cao,Xuemei Jia,Xiangdong Hua,Sujuan Xu,Xiaoguang Liu,Chencheng Dai,Pengfei Xu

doi:10.1038/srep38983

Abstract

Long noncoding RNA (lncRNA) has been recognized as a regulator of gene expression, and the dysregulation of lncRNAs is involved in the progression of many types of cancer, including epithelial ovarian cancer (EOC). To explore the potential roles of lncRNAs in EOC, we performed lncRNA and mRNA microarray profiling in malignant EOC, benign ovarian cyst and healthy control tissues. In this study, 663 transcripts of lncRNAs were found to be differentially expressed in malignant EOC compared with benign and normal control tissues. We also selected 18 altered lncRNAs to confirm the validity of the microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, especially the cell cycle. Furthermore, Series Test of Cluster (STC) and lncRNA-mRNA co-expression network analyses were conducted to predict lncRNA expression trends and the potential target genes of lncRNAs. We also determined that two antisense lncRNAs (RP11-597D13.9 and ADAMTS9-AS1) were associated with their nearby coding genes (FAM198B, ADAMTS9), which participated in cancer progression. This study offers helpful information to understand the initiation and development mechanisms of EOC.

Highlights

Overlapping and intronic lncRNAs according to their genomic localization in relation to nearby coding genes[14]
Benign ovarian cyst and malignant Epithelial ovarian cancer (EOC) tissues were obtained from Nanjing Maternal and Child Health Care Hospital (Supplementary Table S1) and identified by Hematoxylin and Eosin (HE) staining (Supplementary Figure S1)
Heatmaps and scatter-plots were used to assess the variation in lncRNA expression among normal ovarian, benign ovarian cyst and malignant EOC tissues (Fig. 1)

Summary

Introduction

Overlapping and intronic lncRNAs according to their genomic localization in relation to nearby coding genes[14]. A large number of lncRNAs exhibit a tissue- or cell type-specific pattern[15,16] and display weaker evolutionary constraints and lower expression levels than protein-coding genes[17]. A growing body of evidence suggests an important role of lncRNAs in cancer, including EOC. LncRNA expression profiles in malignant EOC will help us to better understand EOC pathogenesis. For candidate lncRNAs that may play potentially important roles in malignant EOC, we examined the Gene Ontology (GO) enrichment of their associated protein-coding genes and performed pathway analyses. Our study confirmed our hypothesis that lncRNAs serve as a new layer of gene regulation in EOC and provided further insight into ovarian tumor therapy

Methods

Results

Conclusion