FOXP4-AS1 is a favorable prognostic-related enhancer RNA in ovarian cancer.

Tian Hua,Yun-Jie Tian,Yun-Hong Kong,Wei Wang,Rui-Qing Tian,Li-Xia Ma,Cai-Fen Zhao,Rui-Min Wang

doi:10.1042/bsr20204008

Abstract

Ovarian cancer (OV) is the main cause of deaths worldwide in female reproductive system malignancies. Enhancer RNAs (eRNAs) are derived from the transcription of enhancers and has attracted increasing attention in cancers recently. However, the biological functions and clinical significance of eRNAs in OV have not been well described presently. We used an integrated data analysis to identify prognostic-related eRNAs in OV. Tissue-specific enhancer-derived RNAs and their regulating genes were considered as putative eRNA–target pairs using the computational pipeline PreSTIGE. Gene expression profiles and clinical data of OV and 32 other cancer types were obtained from the UCSC Xena platform. Altogether, 71 eRNAs candidates showed significant correlation with overall survival (OS) of OV samples (Kaplan–Meier log-rank test, P<0.05). Among which, 23 were determined to be correlated with their potential target genes (Spearman’s r > 0.3, P<0.001). It was found that among the 23 prognostic-related eRNAs, the expression of forkhead box P4 antisense RNA 1 (FOXP4-AS1) had the highest positive correlation with its predicted target gene FOXP4 (Spearman’s r = 0.61). Moreover, the results were further validated by RT-qPCR analysis in an independent OV cohort. Our results suggested the eRNA FOXP4-AS1 expression index may be a favorable independent prognostic biomarker candidate in OV.

Highlights

Ovarian cancer (OV) is the fifth malignant reproductive tumor in women leading to mortality [1]
The results revealed that: (1) for the first time, forkhead box P4 (FOXP4)-AS1 was determined to be an Enhancer RNA (eRNA) with top positive correlation with its target gene FOXP4 among the prognosis-related eRNAs in OV. (2) FOXP4-AS1 may be an independent biomarker in OV patients‘ prognosis
Li et al [26] reported that FOXP4-AS1 and FOXP4 were up-regulated in esophageal carcinoma samples and were positively correlated with each other based on bioinformatics prediction

Summary

Introduction

Ovarian cancer (OV) is the fifth malignant reproductive tumor in women leading to mortality [1]. More and more studies have demonstrated the importance of eRNAs in transcriptional machinery to mediate the target genes transcription [6,7]. Some studies showed that knockdown of the eRNA was associated with the down-regulation of target genes [8,9,10]. The enhancer activation and production of eRNAs were highly associated with the dysregulation of tumor oncogenes, tumor suppressor genes and other stimuli [11,12]. Current models suggested that eRNAs interact with RNA polymerase II (RNA pol II), mediators and transcription factors to promote promoter–enhancer looping and the consequent up-regulation of the corresponding target genes [13]. Research by Li et al [14] pointed out that widely estrogen-induced eRNA transcription was associated with up-regulated corresponding

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