miR-192/215-5p Act as Tumor Suppressors and Link Crohn's Disease and Colorectal Cancer by Targeting Metabolic Pathways: A Comprehensive Database Mining and Experimental Study

Background: MicroRNAs (miRNAs) have emerged as key regulators involved in a variety of biological processes such as inflammatory bowel diseases and tumor progression. Previous studies have demonstrated that miR-192/215 participated in progression of Crohn's disease (CD) and colorectal cancer (CRC), respectively; however, their detailed functional relationships and molecular regulations between two diseases remain unclear. Methods: Here we used bioinformatics methods to systematically expound miR-192/215-5p macrocontrol regulatory networks shared by two diseases. For data mining and validation, several miRNA prediction tools including Tarbase, miRTARBASE, miRecored, miRpathDB, et al; Human miRNA tissue atlas, FunRich, miRcancer, MalaCards, GEPIA, cBioPortal, luciferase assay, et al. are extensively applied. Findings: miR-192/215-5p with identical seed sequence were specially distributed in colon tissues and enriched biological pathways were closely associated with human cancers. Emerging role of miR-192/215-5p in CD and CRC was also analyzed. In addition, we analyzed common pathways targeted by miR-192/215-5p in both diseases. Interpretation: Based on results derived from multiple approaches, we identified the biological functions of miR-192/215-5p as a tumor suppressor and link CD and CRC by targeting triglyceride synthesis and extracellular matrix remodeling pathways. Funding Statement: The research was supported by the Natural Science Foundation of Fujian Province [grant numbers 2012YZ0001-1 and 2016J01582], National Nature Science Foundation of China [grant numbers No.81402107 and No.81601618], Military Medical Science project [grant number No.15QNP025]. Declaration of Interests: No potential conflicts of interest were disclosed. Ethics Approval Statement: The study protocol was approved by the Ethics Committee of Fuzhou General Hospital, Xiamen University. Data collections and processions were performed according to policies of GEO and TCGA project.