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

Cancer Cell International

Milad Shademan¹  Hesam Dehghani¹  Azam Naseri Salanghuch¹  Khadijeh Zare¹  Morteza Zahedi¹  Ladan Goshayeshi²  Kambiz Akhavan Rezayat²  Hooman Mosannen Mozaffari²  Mohammad Ali Foroughi³  Kamran Ghaffarzadegan⁴ 

[1] Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad;Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences;Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad;Pathology Department, Education and Research Department, Razavi Hospital;

关键词: Natural antisense transcripts;    Colorectal adenoma;    Colorectal adenocarcinoma;    Transcription;    PRKCQ-AS1;    SATB1-AS1;   

DOI  :  10.1186/s12935-019-1000-1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown