MiR-92a promotes tumorigenesis of colorectal cancer, a transcriptomic and functional based study

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Accumulation of varieties of epigenetic changes, including miRNA regulation, is one of the fundamental processes driving CRC initiation and progression. Mir-92a has been reported in several studies as an oncogene, and particularly in colorectal cancer, it has become a useful biomarker for early detection of CRC in both serum or stool. The Cancer Genome Atlas (TCGA) is a powerful database to analyze cancer-related genes and their correlation with patients' pathological information. However, miR-92a expression and its regulating target genes has yet to be investigated in TCGA system. In this study, we found miR-92a expression is associated with CRC pathological process. Notably, high expression of miR-92a mainly occurs in microsatellite-stable (MSS) cases. Further experiments showed exogenous introduction of miR-92a into LoVo and SW480 cells could enhance cell proliferation, migration, and invasion, whereas inhibition of miR-92a showed the opposite effects. A system analysis based on binding capacity and expression correlation analysis confirmed DKK3 and KLF4 are the top target genes of miR-92a, and novel target SMAD7 highlights the role of miR-92a in BMPs/SMAD pathway. In conclusion, miR-92a acts as an oncomir and directly targets Wnt/beta-catenin, PTEN/Akt/FoxO, and BMP/Smads related genes, thus participates in CRC progression.