Esophageal cancer (EC) is extremely aggressive and has a very poor survival rate.
Esophageal squamous cell carcinoma (ESCC) accounts for 80% of all ECs worldwide, with the majority of the remaining 20% being esophageal
adenocarcinoma (EAC). Due to its occult and insidious presentation, ESCC is typically diagnosed and treated in its advanced stages, thereby limiting the success of present therapeutic modalities.
microRNAs (
miRNAs) can function as
tumor suppressors or oncogenes, playing critical roles in
cancer initiation and progression by regulating target genes in oncogenic pathways. In the current study, we demonstrated that microRNA-196b (miR-196b) is one of the most upregulated
miRNAs in both ESCC and EAC. miR-196b was overexpressed in ESCC and EAC cell lines, cellular exosomal RNAs, and ESCC tissue samples. Functional studies revealed that miR-196b acted as an oncomiR by directly targeting a
tumor suppressor,
ephrin type-A receptor 7 (EPHA7). EPHA7 abrogates the activity of
ephrin type-A receptor 2 (EPHA2), a key molecule involved in the epithelial-to-mesenchymal transition (EMT) and MAPK/ERK pathways, mediating resistance to UV and
chemoradiotherapy in both ESCC and EAC. Taken together, these findings suggest that miR-196b is a strong candidate molecular target for EC treatment.