TY - JOUR
T1 - Pyknon-Containing Transcripts Are Downregulated in Colorectal Cancer Tumors, and Loss of PYK44 Is Associated With Worse Patient Outcome
AU - Evangelista, Adriane Feijó
AU - de Menezes, Weder Pereira
AU - Berardinelli, Gustavo Noriz
AU - Dos Santos, Wellington
AU - Scapulatempo-Neto, Cristovam
AU - Guimarães, Denise Peixoto
AU - Calin, George A.
AU - Reis, Rui Manuel
N1 - Funding Information:
We thank Barretos Cancer Hospital Biobank for technical assistance for nucleic acid isolation. Funding. This work was supported by Brazilian agencies FAPESP (process nr# 2013/15515-6), Fellowships from CAPES, FINEP (MCTI/FINEP/MS/SCTIE/DECIT), Public Ministry of Labor Campinas (Research, Prevention and Education of Occupational Cancer, Brazil), and MD Anderson Cancer Center (USA) SINF (Sister Institution Network Fund) grant.
Publisher Copyright:
© Copyright © 2020 Evangelista, de Menezes, Berardinelli, Dos Santos, Scapulatempo-Neto, Guimarães, Calin and Reis.
PY - 2020/11/12
Y1 - 2020/11/12
N2 - Pyknons are specific human/primate-specific DNA motifs at least 16 nucleotides long that are repeated in blocks in intergenic and intronic regions of the genome and can be located in a new class of non-coding RNAs of variable length. Recent studies reported that pyknon deregulation could be involved in the carcinogenesis process, including colorectal cancer. We evaluated the expression profile of a set of 12 pyknons in a set of molecularly characterized colorectal cancer (CRC) patients. The pyknons (PYK10, PYK14, PYK17, PYK26, PYK27, PYK40, PYK41, PYK42, PYK43, PYK44, PYK83, and PYK90) expression was determined by qRT-PCR. A pilot analysis of 20 cases was performed, and consistent results were obtained for PYK10, PYK17, PYK42, PYK44, and PYK83. Further, the expression of the selected pyknons was evaluated in 73 CRC cases. Moreover, in 52 patients, we compared the expression profile in both tumor and normal tissues. All five pyknons analyzed showed significantly lower expression levels in the tumor compared to normal tissue. It was observed an association between expression of PYK10 with TP53 mutations (p = 0.029), PYK17 to histologic grade (p = 0.035), and PYK44 to clinical staging (p = 0.016). Moreover, levels of PYK44 were significantly associated with the patient's poor overall survival (p = 0.04). We reported the significant downregulation of pyknons motifs in tumor tissue compared with the normal counterpart, and the association of lower PYK44 expression with worse patient outcome. Further studies are needed to extend and validate these findings and determine the clinical-pathological impact.
AB - Pyknons are specific human/primate-specific DNA motifs at least 16 nucleotides long that are repeated in blocks in intergenic and intronic regions of the genome and can be located in a new class of non-coding RNAs of variable length. Recent studies reported that pyknon deregulation could be involved in the carcinogenesis process, including colorectal cancer. We evaluated the expression profile of a set of 12 pyknons in a set of molecularly characterized colorectal cancer (CRC) patients. The pyknons (PYK10, PYK14, PYK17, PYK26, PYK27, PYK40, PYK41, PYK42, PYK43, PYK44, PYK83, and PYK90) expression was determined by qRT-PCR. A pilot analysis of 20 cases was performed, and consistent results were obtained for PYK10, PYK17, PYK42, PYK44, and PYK83. Further, the expression of the selected pyknons was evaluated in 73 CRC cases. Moreover, in 52 patients, we compared the expression profile in both tumor and normal tissues. All five pyknons analyzed showed significantly lower expression levels in the tumor compared to normal tissue. It was observed an association between expression of PYK10 with TP53 mutations (p = 0.029), PYK17 to histologic grade (p = 0.035), and PYK44 to clinical staging (p = 0.016). Moreover, levels of PYK44 were significantly associated with the patient's poor overall survival (p = 0.04). We reported the significant downregulation of pyknons motifs in tumor tissue compared with the normal counterpart, and the association of lower PYK44 expression with worse patient outcome. Further studies are needed to extend and validate these findings and determine the clinical-pathological impact.
KW - Brazilian population
KW - TP53 mutations
KW - colorectal cancer
KW - gene expression regulation
KW - non-coding RNAs
KW - pyknons
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UR - http://www.scopus.com/inward/citedby.url?scp=85096678075&partnerID=8YFLogxK
U2 - 10.3389/fgene.2020.581454
DO - 10.3389/fgene.2020.581454
M3 - Article
C2 - 33304384
AN - SCOPUS:85096678075
SN - 1664-8021
VL - 11
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 581454
ER -