Synergism of HPV and MNNG repress miR-218 promoting Het-1A cell malignant transformation by targeting GAB2.

Dysregulation of microRNAs (miRNAs) is induced during tumorigenesis. Our previous research suggested that HPV and MNNG led to malignant transformation of esophageal epithelial cells. To investigate the regulation and function of miR-218(miR-218-5p) during the malignant transformation of esophageal epithelial cells, we found miR-218 was inhibited synergistically by HPV and MNNG, suppressing cell proliferation, migration and invasion by up-regulating 3' untranslated region (3'UTR) GAB2 in Het-1A-HPV-MNNG cells (malignant Het-1A cells induced by HPV and MNNG). A negative correlation was found between miR-218 and GAB2 mRNA expression in esophageal cancer patients and control people. GAB2 was up-regulated in Het-1A-HPV-MNNG cells. Further, down-expression of GAB2 reversed HPV&MNNG-mediated activation of migration and invasion and repressed SHP2/ERK and Akt/mTOR pathway signaling. In conclusion, miR-218 partially accounts for the prevention effect during malignant transformation of normal esophageal epithelial cells, which targets GAB2, which supplies the potential treatment in cancer therapy.