Transcript CD81‐215 may be a long noncoding RNA of stromal origin with tumor‐promoting role in colon cancer

• Published in: Cell biochemistry and function 2023-12, Vol.41 (8), p.1503-1513
• Main Authors: Jovanovic, Emilija, Babic, Tamara, Dragicevic, Sandra, Kmezic, Stefan, Nikolic, Aleksandra
• Format: Article
• Language: English
• Subjects: Biomarkers; Carcinogenesis; Carcinogens; CD81; CD81 antigen; Colon; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Colorectal cancer; Colorectal carcinoma; Gene expression; Gene Expression Profiling; gene promoter; Gene sequencing; Genetic transformation; Genomes; Humans; Localization; Mucosa; Non-coding RNA; Precision medicine; Promoters; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; Signal Transduction; Structure-function relationships; Tetraspanin 28 - genetics; Tetraspanin 28 - metabolism; Therapeutic targets; transcriptome; Transcriptomes; Tumors
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.3890

The role of tetraspanin CD81 in malignant transformation is best studied in colorectal cancer, and it appears that other transcripts beside the fully coding mRNA may also be dysregulated in malignant cells. Recent data from a comprehensive pan‐cancer transcriptome analysis demonstrated differential activity of two alternative CD81 gene promoters in malignant versus nonmalignant gut mucosa. The promoter active in gut mucosa gives rise to transcripts CD81‐203 and CD81‐213, while the promoter active in colon and rectal cancer gives rise to transcripts CD81‐205 and CD81‐215. Our study aimed to explore the biomarker potential of the transcripts from the alternative CD81 gene promoters in colon cancer, as well as to investigate their structure and potential function using in silico tools. The analysis of the transcripts' expression in several colon cell lines cultivated in 2D and 3D and a set of colon cancer and healthy gut mucosa samples by qPCR and RNA sequencing suggested their low expression and stromal origin. Expression patterns in tumor and nontumor tissue along with in silico data suppose that the transcript CD81‐215 may be a noncoding RNA of stromal origin with possible involvement in signaling related to malignant transformation. Significance statement Elements of the noncoding transcriptome are increasingly being accepted as the factors contributing to the complexity of the genome, but their role remains unexplored in spite of demonstrated relevance for many diseases, including cancer. Noncoding transcripts harbor vast potential for application in personalized medicine, both as prospective therapeutics and therapeutic targets. The differential expression of the transcript CD81‐215 in tumor and nontumor tissue, along with in silico predictions of its structure, localization, and interaction partners, point to the possible involvement of this molecule in colorectal carcinogenesis and its biomarker potential.