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

Mina Zamani; Ali-Mohammad Foroughmand; Mohammad-Reza Hajjari; Babak Bakhshinejad; Rory Johnson; Hamid Galehdari

doi:10.3389/fonc.2022.954634

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

Front Oncol. 2022 Aug 16:12:954634. doi: 10.3389/fonc.2022.954634. eCollection 2022.

Authors

Mina Zamani¹, Ali-Mohammad Foroughmand¹, Mohammad-Reza Hajjari¹, Babak Bakhshinejad², Rory Johnson^{3

4

5

6}, Hamid Galehdari¹

Affiliations

¹ Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
² Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
³ Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ Department for BioMedical Research, University of Bern, Bern, Switzerland.
⁵ School of Biology and Environmental Science, University College Dublin, Dublin, Ireland.
⁶ Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.

Abstract

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 MYC locus. It seems that MYC is not the only target of these alterations. The MYC-proximal mutations may act via regulatory noncoding RNAs (ncRNAs). In this study, gene expression analyses indicated that the expression of some PVT1 spliced linear transcripts, CircPVT1, CASC11, and MYC is increased in colorectal cancer (CRC). Moreover, the expression of these genes is associated with some clinicopathological characteristics of CRC. Also, in vitro studies in CRC cell lines demonstrated that CASC11 is mostly detected in the nucleus, and different transcripts of PVT1 have different preferences for nuclear and cytoplasmic parts. Furthermore, perturbation of PVT1 expression and concomitant perturbation in PVT1 and CASC11 expression caused MYC overexpression. It seems that transcription of MYC 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 MYC regulation network and in the carcinogenesis of colorectal cells.

Keywords: 8q24; CASC11; MYC; PVT1; colorectal cancer; noncoding RNA.