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

AIMS

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.

MAIN 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.

KEY FINDINGS

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.

SIGNIFICANCE

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