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Deregulation of H19 is associated with cervical carcinoma

Roychowdhury, Anirban, Samadder, Sudip, Das, Pijush, Mazumder, Dipanjana Indra, Chatterjee, Ankita, Addya, Sankar, Mondal, Ranajit, Roy, Anup, Roychoudhury, Susanta, Panda, Chinmay Kumar
Genomics 2020 v.112 no.1 pp. 961-970
gene expression regulation, gene overexpression, methylation, microarray technology, patients, prognosis, pseudogenes, quantitative polymerase chain reaction, transcription (genetics), uterine cervical neoplasms, women
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.