AUTHOR=Evangelista Adriane Feijó , de Menezes Weder Pereira , Berardinelli Gustavo Noriz , Dos Santos Wellington , Scapulatempo-Neto Cristovam , Guimarães Denise Peixoto , Calin George A. , Reis Rui Manuel 

TITLE=Pyknon-Containing Transcripts Are Downregulated in Colorectal Cancer Tumors, and Loss of PYK44 Is Associated With Worse Patient Outcome

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.581454

DOI=10.3389/fgene.2020.581454

ISSN=1664-8021

ABSTRACT=<p>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 (<italic>PYK10</italic>, <italic>PYK14</italic>, <italic>PYK17</italic>, <italic>PYK26</italic>, <italic>PYK27</italic>, <italic>PYK40</italic>, <italic>PYK41</italic>, <italic>PYK42</italic>, <italic>PYK43</italic>, <italic>PYK44</italic>, <italic>PYK83</italic>, and <italic>PYK90</italic>) expression was determined by qRT-PCR. A pilot analysis of 20 cases was performed, and consistent results were obtained for <italic>PYK10</italic>, <italic>PYK17</italic>, <italic>PYK42</italic>, <italic>PYK44</italic>, and <italic>PYK83</italic>. 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 <italic>PYK10</italic> with <italic>TP53</italic> mutations (<italic>p</italic> = 0.029), <italic>PYK17</italic> to histologic grade (<italic>p</italic> = 0.035), and <italic>PYK44</italic> to clinical staging (<italic>p</italic> = 0.016). Moreover, levels of <italic>PYK44</italic> were significantly associated with the patient's poor overall survival (<italic>p</italic> = 0.04). We reported the significant downregulation of pyknons motifs in tumor tissue compared with the normal counterpart, and the association of lower <italic>PYK44</italic> expression with worse patient outcome. Further studies are needed to extend and validate these findings and determine the clinical-pathological impact.</p>