miR-135a Inhibits the Invasion and Migration of Esophageal Cancer Stem Cells through the Hedgehog Signaling Pathway by Targeting Smo.

Cancer stem cells (CSCs) have been reported to be involved in esophageal cancer (EC) development. Hence, we aim to explore whether microRNA-135a (miR-135a) affects EC and its associated mechanism. Cancerous and adjacent tissues from 138 EC patients were collected. The dual-luciferase reporter gene assay and bioinformatics analysis were used to confirm the interaction between nucleotides. A series of mimics or inhibitors of miR-135a or small interfering RNA (siRNA) against Smo were introduced into EC cells. After that, the expression of miR-135a and Hedgehog (Hh) signaling pathway-related genes (Smo, Gli1, Shh, and Gli2) in tissues and cells was measured, accompanied by evaluation of cell viability, apoptosis, invasion, and migration. High expression of Smo, Gli1, Shh, and Gli2 and low expression of miR-135a were observed in EC. Smo was verified to be a target gene of miR-135a. In addition, overexpression of miR-135a or silencing of Smo decreased the expression of Gli1, Gli2, and Shh, thus inhibiting EC cell proliferation, migration, and invasion and promoting apoptosis. Silencing of miR-135a was observed to reverse the inhibitory role of miR-135a in EC. These results suggest that miR-135a inhibited the migration and invasion of EC cells through inhibition of the Smo/Hh axis.