A novel microRNA located in the gene regulates the Wnt signaling pathway and is differentially expressed in colorectal cancer specimens.

Tropomyosin receptor kinase C () is involved in cell survival, apoptosis, differentiation, and tumorigenesis. diverse functions might be attributed to the hypothetical non-coding RNAs embedded within the gene. Using bioinformatics approaches, a novel microRNA named was predicted within the gene capable of regulating the Wnt pathway. For experimental verification of this microRNA, the predicted sequence was overexpressed in SW480 cells, which led to the detection of two mature isomiRs, and their endogenous forms were detected in human cell lines as well. Later, an independent promoter was deduced for after the treatment of HCT116 cells with 5-azacytidine, which resulted in differential expression of and host gene. RT-quantitative PCR and luciferase assays indicated that the gene is targeted by , and Wnt signaling is up-regulated. Also, Wnt inhibition by using small molecules along with overexpression and TOP/FOP flash assays confirmed the positive effect of on the Wnt pathway. Consistently, overexpression promoted SW480 cell survival, which was detected by flow cytometry, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, and crystal violate analysis. RT-qPCR analysis revealed that is significantly up-regulated (∼70 times) in colorectal tumor tissues compared with their normal pairs. Moreover, the expression level discriminated grades of tumor malignancies, which was consistent with its endogenous levels in HCT116, HT29, and SW480 colorectal cancer cell lines. Finally, an opposite expression pattern was observed for and the gene in colorectal cancer specimens. In conclusion, here we introduce as a novel regulator of Wnt signaling, which might be a candidate oncogenic colorectal cancer biomarker.