Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by increasing its cognate gene PHB expression.
Pseudogene PHBP1 promotes esophageal squamous cell carcinoma proliferation by increasing its cognate gene PHB expression.
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DOI：
10.18632/oncotarget.16196
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发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Gao S
中科院分区：
文献类型：
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作者：
Feng F;Qiu B;Zang R;Song P;Gao S
天然反义转录物（Natural antisense transcripts，NAT）是一类种类最多的长链非编码RNA（long noncoding RNA，lncRNA），参与了人类的重要生理过程。在此，我们报道了人抑制素基因假基因1（PHBP 1）在食管鳞癌中表达上调，且PHBP 1表达增加与临床晚期相关。功能性实验表明，PHBP 1基因敲低抑制食管鳞癌细胞增殖，集落形成和异种移植瘤生长在体外和体内引起细胞周期停滞在G1-G 0期。机制分析表明，PHBP 1作为一种反义转录本，与PHBmRNA部分互补，形成RNA-RNA杂交体，从而在mRNA和蛋白水平诱导PHBmRNA表达增加。此外，PHBP 1的表达与食管鳞癌组织中的PHB表达密切相关。总的来说，这项研究阐明了PHBP 1在促进ESCC中的重要作用，部分通过增加PHB的表达。
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.