Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by increasing its cognate gene PHB expression

Feiyue Feng,Peng Song,Shugeng Gao,Ruochuan Zang,Bin Qiu

doi:10.18632/oncotarget.16196

Abstract

Natural antisense transcripts (NATs) as one of the most diverse classes of long noncoding RNAs (lncRNAs), have been demonstrated involved in fundamental biological processes in human. Here, we reported that human prohibitin gene pseudogene 1 (PHBP1) was upregulated in ESCC, and increased PHBP1 expression in ESCC was associated with clinical advanced stage. Functional experiments showed that PHBP1 knockdown inhibited ESCC cells proliferation, colony formation and xenograft tumor growth in vitro and in vivo by causing cell-cycle arrest at the G1-G0 phase. Mechanisms analysis revealed that PHBP1 transcript as an antisense transcript of PHB is partially complementary to PHB mRNA and formed an RNA-RNA hybrid with PHB, consequently inducing an increase of PHB expression at both the mRNA and protein levels. Furthermore, PHBP1 expression is strongly correlated with PHB expression in ESCC tissues. Collectively, this study elucidates an important role of PHBP1 in promoting ESCC partly via increasing PHB expression.

Highlights

In the past decades, esophageal squamous cell carcinoma (ESCC), as the most common type of esophageal cancer, has been one of the most leading causes of cancer-related death worldwide [1, 2]
prohibitin gene pseudogene 1 (PHBP1), which is transcribed in antisense orientation with respect to prohibitin gene (PHB) and shared the high level of the nucleotide sequence identity with its cognate gene PHB
We investigated PHBP1 and PHB expression in an independent cohort of ESCC tissues and normal tissues

Summary

Introduction

Esophageal squamous cell carcinoma (ESCC), as the most common type of esophageal cancer, has been one of the most leading causes of cancer-related death worldwide [1, 2]. A plenty of evidence has proved that lncRNAs play essential roles in fundamental biological processes, such as cell growth, differentiation, immune response and cancer biology [10,11,12,13,14,15,16,17,18,19]. One group of lncRNAs is the natural antisense transcripts (NATs), accounting for about 50-70% of lncRNAs, transcribed from the opposite DNA strand of their endogenous sense counterpart’s proteincoding genes and non-protein-coding genes [20, 21]. Antisense lncRNAs (aslncRNAs) have garnered increased attention due to their highly locus-specific effects. One major emerging theme is centered on the effects of aslncRNAs exerting in cis on their neighboring genes or in trans on other distant genes through transcriptional or posttranscriptional regulation [26, 27]

Methods

Results

Conclusion