Long non-coding RNA ZFAS۱: Functions and mechanisms in colorectal cancer

Introduction and Objective: Colorectal cancer (CRC) is the fourth greatest cause of cancer-related death worldwide giving rise to ۶۰۰,۰۰۰ deaths per year. Therefore, it’s important to understand the molecular factors involved in the development of this cancer, one of these factors is long non-coding RNA (LncRNA). LncRNAs are a type of non-coding RNA which involved in the development of cancer. Zinc Finger NFX۱-Type Containing ۱ (ZNFX۱) antisense RNA ۱ (ZFAS۱) is a long non-coding RNA on chromosome ۲۰q۱۳.۱۳. All previous studies have demonstrated that ZFAS۱ is up-regulated and acts as an oncogene in colorectal cancer. So, this article was written to better understand the functions of ZFAS۱.Method: The articles have been collected by searching the following databases: PubMed, Scopus and google scholar.Results: This lncRNA functions as an oncogene by directly binding to DDX۲۱ and affecting the stability and translation of its downstream target gene, POLR۱B, enhancing CRC cell proliferation, migration, invasion, and reducing cell apoptosis. Additionally, SREBP۱ mRNA is stabilized by binding ZFAS۱ to PABP۲ resulting in enhancing SREBP۱ expression and its target genes including stearoyl-CoA desaturase (SCD۱) and fatty acid synthase (FASN). So, this lncRNA and its downstream targets are involved in fat metabolism. Furthermore, it has been discovered that disruption of lipid metabolism aids in the growth of CRC. Also, ZFAS۱ can destroy the p۵۳ protein and the CDK۱/cyclin B۱ complex, which are responsible for cell cycle progress and apoptosis inhibition. Another function of ZFAS۱ is sponging the tumor suppressors miR-۷-۵p, miR-۴۸۴, and miR-۱۵۰-۵p. miR-۷-۵p suppresses CRC progression via the PI۳K/Akt/mTOR signaling pathway. miR-۴۸۴ inhibited proliferation and the transition between epithelial and mesenchymal cells. By specifically targeting VEGFA, miR-۱۵۰-۵p was discovered to be a negative regulator of vascular endothelial growth factor A (VEGFA), resulting in reduced angiogenesis, migration, and proliferation of cells.Conclusion: The ZFAS۱ acts as an oncogene and contributes to the development of colorectal cancer malignancies, cell migration, and proliferation. Therefore, this lncRNA can be a novel therapeutic and diagnostic target in colorectal cancer.

کلیدواژه ها:

LncRNA ، ZFAS۱ ، colorectal cancer ، miRNA