Feng Feiyue, Qiu Bin, Zang Ruochuan, Song Peng, Gao Shugeng
Department of Thoracic Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Oncotarget. 2017 Apr 25;8(17):29091-29100. doi: 10.18632/oncotarget.16196.
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.
天然反义转录本（NATs）作为长链非编码RNA（lncRNAs）中最多样化的类别之一，已被证明参与人类的基本生物学过程。在此，我们报道人类抑制素基因假基因1（PHBP1）在食管癌中上调，且食管癌中PHBP1表达增加与临床晚期相关。功能实验表明，敲低PHBP1可通过使细胞周期停滞在G1-G0期来抑制食管癌细胞在体外和体内的增殖、集落形成及异种移植瘤生长。机制分析显示，PHBP1转录本作为PHB的反义转录本，与PHB mRNA部分互补并与PHB形成RNA-RNA杂交体，从而导致PHB在mRNA和蛋白质水平上的表达均增加。此外，在食管癌组织中，PHBP1表达与PHB表达密切相关。总体而言，本研究阐明了PHBP1通过部分增加PHB表达在促进食管癌发生中所起的重要作用。
