Positioning in 8q24.21 Involved in the Tumorigenesis of Colorectal Cancer by Targeting .

Background: Colorectal cancer remains to be the third leading cause of cancer mortality rates. Despite the diverse effects of the miRNA cluster located in of 8q24.21 across various tumors, the specific biological function in colorectal cancer has not been clarified.

Methods: The amplification of the cluster was analyzed with the cBioPortal database, while the expression and survival analysis of the miRNAs in the cluster were obtained from several GEO databases of colorectal cancer. To investigate the functional role of in colorectal cancer, overexpression and silencing experiments were performed by mimic and inhibitor transfection in colorectal cancer cell lines, respectively. Then, the effects of miR-1204 on cell proliferation were assessed through CCK-8, colony formation, and Edu assay. In addition, cell migration was evaluated using wound healing and Transwell assay. Moreover, candidate genes identified through RNA sequencing and predicted databases were identified and validated using PCR and western blot. A Dual-luciferase reporter experiment was conducted to identify as the target gene of .

Results: In colorectal cancer, the cluster exhibited high amplification, and the expression levels of several cluster miRNAs were also significantly increased. Furthermore, was found to be significantly associated with disease-specific survival according to the analysis of GSE17536. Functional experiments demonstrated that transfection of mimic or inhibitor could enhance or decrease cancer cell proliferation and migration. was identified as a target of . Additionally, the overexpression of partially rescued the effect of mimics on tumorigenic abilities in LOVO cells.

Conclusion: positioning in 8q24.21 promotes the proliferation and migration of colorectal cancer cells by targeting .