Induction of let-7e gene expression attenuates oncogenic phenotype in HCT-116 colorectal cancer cells through targeting of DCLK1 regulation.

Objective: MicroRNAs (miRNAs) are small noncoding RNAs that negatively control gene expression at the translational level. There are compelling evidences indicating that the expression of let-7e is downregulated in various cancers, however, the role of let-7e in colorectal cancer (CRC) and its mechanism has been remained unknown. Here, we investigated the potential role of let-7e in regulating CRC cells phenotypes.

Methods: Let-7e and DCLK1 siRNA were transfected in HCT-116 cells. Colony formation assay, scratch test, Annexin V/PI flow cytometry, and sphere formation assay were performed to examine the cell proliferation, migration, apoptosis, and stemness, respectively. The expression of let-7e, epithelial-mesenchymal transition (EMT)-related genes, Doublecortin like kinase protein 1 (DCLK1), and cancer stem cells (CSCs) were assessed using RT-qPCR while the protein level of DCLK1 was determined by western blotting.

Results: Overexpression of let-7e effectively inhibited cell proliferation, suppressed migration, reduced sphere formation, and precluded EMT process as well as stemness factors. Furthermore, let-7e suppressed DCLK1 expression. Additionally, we found that the expression of let-7e was negatively correlated with DCLK1 expression in CRC cells.

Conclusions: Let-7e plays an important role as tumor suppressor miRNA in CRC probably through inhibition of DCLK1 expression.