Expression profile analysis of two antisense lncRNAs to improve prognosis prediction of colorectal adenocarcinoma

Shademan, M. and Salanghuch, A. N. and Zare, K. and Zahedi, M. and Foroughi, M. A. and Rezayat, K. A. and Mozaffari, H. M. and Ghaffarzadegan, K. and Goshayeshi, L. and Dehghani, H. (2019) Expression profile analysis of two antisense lncRNAs to improve prognosis prediction of colorectal adenocarcinoma. Cancer Cell International, 19 (1).

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Abstract

Background: Long noncoding RNAs (lncRNAs) are involved in different pathogenesis pathways including cancer pathogenesis. The adenoma-carcinoma pathway in colorectal cancer may involve the aberrant and variable gene expression of regulatory RNAs. This study was conducted to analyse the expression and prognosis prediction ability of two natural antisense transcripts, protein kinase C theta antisense RNA 1 (PRKCQ-AS1), and special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) in colorectal low-grade adenoma, advanced adenoma, and adenocarcinomas. Methods: In this study, from two RNA-seq analyses of CCAT1-ko cells and colorectal carcinoma biopsies having diminished and increased levels of CCAT1 transcription, respectively, we nominated two antisense lncRNAs of PRKCQ-AS1 and SATB1-AS1. Samples from colorectal low-grade adenomas, advanced adenomas, adenocarcinomas, and adjacent tissue were subjected to RT-qPCR to determine the expression of PRKCQ-AS1, SATB1-AS1 along with colon cancer-associated transcript 1 (CCAT1) and cMYC. In addition, we used different bioinformatics analyses and webservers (including GEPIA 2, TCGA, and CancerMine) to elucidate the prognosis prediction value, the expression correlation of sense-antisense pair of genes, and the expression profile of these antisense transcripts at the presence or absence of mutations in the driver genes, or the corresponding sense genes. Results: PRKCQ-AS1 showed a wide range of expression levels in colorectal adenoma, advanced adenoma, and adenocarcinoma. Upregulation of PRKCQ-AS1 was related to a significant decrease in survival of colorectal cancer (CRC) patients. The expression levels of PRKCQ-AS1 and PRKCQ were strong and significantly concordant in normal and cancerous colorectal tissues. While SATB1-AS1 showed a wide range of expression in colorectal adenoma, advanced adenoma, and adenocarcinoma as well, its expression was not related to a decrease in survival of CRC patients. The expression levels of SATB1-AS1 and SATB1 (the sense gene) were not strong in normal colorectal tissues. In addition, where SATB1 gene was mutated, the expression of SATB1-AS1 was significantly downregulated. Conclusions: We found the expression of PRKCQ-AS1 and SATB1-AS1 at a given stage of CRC very variable, and not all biopsy samples showed the increased expression of these antisense transcripts. PRKCQ-AS1 in contrast to SATB1-AS1 showed a significant prognostic value. Since a significantly concordant expression was observed for SATB1-AS1 and SATB1 in only cancerous, and for PRKCQ-AS1 and PRKCQ in both normal and cancerous colorectal tissues, it can be concluded that common mechanisms may regulate the expression of these sense and antisense genes. © 2019 The Author(s).

Item Type: Article
Additional Information: Export Date: 16 February 2020 CODEN: CCIAC Correspondence Address: Goshayeshi, L.; Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical SciencesIran; email: goshayeshiL@mums.ac.ir
Uncontrolled Keywords: Colorectal adenocarcinoma Colorectal adenoma Natural antisense transcripts PRKCQ-AS1 SATB1-AS1 Transcription long untranslated RNA protein kinase C theta antisense RNA 1 special AT-rich sequence binding protein 1 antisense RNA 1 unclassified drug Article cancer grading cancer prognosis cancer staging cancer survival carcinogenesis CCAT1 gene cohort analysis colorectal cancer cell line colorectal carcinoma controlled study down regulation gene gene expression profiling gene expression regulation gene mutation human human cell human tissue oncogene c myc PRKCQ-AS1 gene real time reverse transcription polymerase chain reaction rectum biopsy RNA sequence RNA transcription SATB1-AS1 gene upregulation
Subjects: W General medicine- Health professions
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib1 lib1
Date Deposited: 27 Jun 2020 05:38
Last Modified: 27 Jun 2020 05:38
URI: http://eprints.mums.ac.ir/id/eprint/18636

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