AUTHOR=Zamani Mina , Foroughmand Ali-Mohammad , Hajjari Mohammad-Reza , Bakhshinejad Babak , Johnson Rory , Galehdari Hamid 

TITLE=CASC11 and PVT1 spliced transcripts play an oncogenic role in colorectal carcinogenesis

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.954634

DOI=10.3389/fonc.2022.954634

ISSN=2234-943X

ABSTRACT=<p>Cancer is fundamentally a genetic disorder that alters cellular information flow toward aberrant growth. The coding part accounts for less than 2% of the human genome, and it has become apparent that aberrations within the noncoding genome drive important cancer phenotypes. The numerous carcinogenesis-related genomic variations in the 8q24 region include single nucleotide variations (SNVs), copy number variations (CNVs), and viral integrations occur in the neighboring areas of the <italic>MYC</italic> locus. It seems that <italic>MYC</italic> is not the only target of these alterations. The <italic>MYC</italic>-proximal mutations may act <italic>via</italic> regulatory noncoding RNAs (ncRNAs). In this study, gene expression analyses indicated that the expression of some <italic>PVT1</italic> spliced linear transcripts, <italic>CircPVT1</italic>, <italic>CASC11</italic>, and <italic>MYC</italic> is increased in colorectal cancer (CRC). Moreover, the expression of these genes is associated with some clinicopathological characteristics of CRC. Also, <italic>in vitro</italic> studies in CRC cell lines demonstrated that <italic>CASC11</italic> is mostly detected in the nucleus, and different transcripts of <italic>PVT1</italic> have different preferences for nuclear and cytoplasmic parts. Furthermore, perturbation of <italic>PVT1</italic> expression and concomitant perturbation in <italic>PVT1</italic> and <italic>CASC11</italic> expression caused <italic>MYC</italic> overexpression. It seems that transcription of <italic>MYC</italic> is under regulatory control at the transcriptional level, i.e., initiation and elongation of transcription by its neighboring genes. Altogether, the current data provide evidence for the notion that these noncoding transcripts can significantly participate in the <italic>MYC</italic> regulation network and in the carcinogenesis of colorectal cells.</p>