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

Oncotarget. 2017 Apr 25;8(17):29091-29100. 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.

Keywords: SDS-polyacrylamide gel electrophoresis (SDS-PAGE); esophageal squamous cell carcinoma (ESCC); long noncoding RNA (lncRNA); natural antisense transcript (NAT); quantitative real-time PCR (qRT-PCR).

MeSH terms

  • Aged
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Staging
  • Prohibitins
  • Pseudogenes / genetics*
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • PHB protein, human
  • Prohibitins
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Small Interfering
  • Repressor Proteins