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并且剪接转录本在结直肠癌发生过程中发挥致癌作用。

and spliced transcripts play an oncogenic role in colorectal carcinogenesis.

作者信息

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

机构信息

Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

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

DOI:10.3389/fonc.2022.954634
PMID:36052265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9424822/
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 locus. It seems that is not the only target of these alterations. The -proximal mutations may act regulatory noncoding RNAs (ncRNAs). In this study, gene expression analyses indicated that the expression of some spliced linear transcripts, , , and is increased in colorectal cancer (CRC). Moreover, the expression of these genes is associated with some clinicopathological characteristics of CRC. Also, studies in CRC cell lines demonstrated that is mostly detected in the nucleus, and different transcripts of have different preferences for nuclear and cytoplasmic parts. Furthermore, perturbation of expression and concomitant perturbation in and expression caused overexpression. It seems that transcription of 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 regulation network and in the carcinogenesis of colorectal cells.

摘要

癌症从根本上来说是一种基因紊乱疾病,它会改变细胞信息流,导致异常生长。编码部分占人类基因组的比例不到2%,很明显,非编码基因组内的畸变驱动着重要的癌症表型。8q24区域内众多与致癌作用相关的基因组变异包括单核苷酸变异(SNV)、拷贝数变异(CNV),并且病毒整合发生在该位点的邻近区域。似乎 并非这些改变的唯一靶点。 -近端突变可能作用于调控性非编码RNA(ncRNA)。在本研究中,基因表达分析表明,一些剪接的线性转录本、、和在结直肠癌(CRC)中的表达增加。此外,这些基因的表达与CRC的一些临床病理特征相关。同样,在CRC细胞系中的研究表明, 主要在细胞核中检测到,并且 的不同转录本对细胞核和细胞质部分有不同的偏好。此外, 表达的扰动以及 和 表达的伴随扰动导致 过表达。似乎 的转录在转录水平上受到调控,即受其邻近基因对转录起始和延伸的调控。总之,目前的数据为这些非编码转录本可显著参与 调控网络以及结直肠细胞致癌作用这一观点提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/de1f6e118835/fonc-12-954634-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/93110abee9ce/fonc-12-954634-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/33692163ce68/fonc-12-954634-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/73dbe58f3ba7/fonc-12-954634-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/1eb41dfc4f67/fonc-12-954634-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/33bbe355bd04/fonc-12-954634-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/de1f6e118835/fonc-12-954634-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/93110abee9ce/fonc-12-954634-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/33692163ce68/fonc-12-954634-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/73dbe58f3ba7/fonc-12-954634-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/1eb41dfc4f67/fonc-12-954634-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/33bbe355bd04/fonc-12-954634-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b60b/9424822/de1f6e118835/fonc-12-954634-g006.jpg

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The PVT1 lncRNA is a novel epigenetic enhancer of MYC, and a promising risk-stratification biomarker in colorectal cancer.PVT1 lncRNA 是 MYC 的新型表观遗传增强子,也是结直肠癌有前景的风险分层生物标志物。
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