Deregulation of H19 is associated with cervical carcinoma

Genomics. 2020 Jan;112(1):961-970. doi: 10.1016/j.ygeno.2019.06.012. Epub 2019 Jun 21.

Abstract

CACX is one of the most common cancer affecting women world-wide. Here, expression microarray analysis revealed 8 over-expressed transcribed pseudogenes (GBP1P1, HLA-DRB6, HLA-H, SLC6A10P, NAPSB, KRT16P2, PTTG3P and RNF126P1), down-regulated 7 lincRNAs (H19, MIR100HG, MEG3, DIO3OS, HOXA11-AS, CD27-AS1 and EPB41L4A-AS) and 6 snoRNAs (SNORD97, SNORD3A, SNORD3C, SNORD3D, SNORA12 and SCARNA9) as DEncGs (log2 fold-change ≥ ±1.0) in CACX. Consequently, down-regulation of lincRNA MEG3 and over-expression of pseudogenes, GBP1P1 and PTTG3P in the microarray analysis were found concordant with the real-time quantitative PCR results upon validation. Then, Ingenuity® Pathway analysis (IPA®) analysis with deregulated DEncGs identified functionally important gene, H19. Further, validation (n = 52) of expression confirmed frequent downregulation of H19 with significant association with its deletion (LOH) and promoter methylation (n = 128) in CACX. Moreover, clinicopathological analysis found Indian CACX patients (n = 26) with alterations of H19 by deletion or, promoter methylation with concomitant low expression have poor prognosis.

Keywords: Cervical cancer; H19; Long intergenic non-coding RNAs; Non-coding RNAs; Patient prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Cell Line, Tumor
  • DNA Methylation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • India
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Promoter Regions, Genetic
  • Pseudogenes
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Nucleolar / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology

Substances

  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • RNA, Small Nucleolar