MYCN-mediated miR-21 overexpression enhances chemo-resistance via targeting CADM1 in tongue cancer

Chemo-resistance is still a major obstacle in successful cancer treatment. previously, we found that mir-21 (mir-21-5p) was upregulated in drug-resistant tongue cancer (tc) cell line tca8113/pym. however, the mechanisms for mir-21 upregulation and its role in chemo-resistance in tc remain unclear. here, we demonstrated that functional inhibition of mir-21 sensitized tc cells to chemotherapy. in agreement, overexpressed mir-21 enhanced chemo-resistance in tc cells. we found that mir-21 directly targeted cadm1 expression, which was downregulated in drug-resistant tc cells. restored cadm1 expression sensitized tc cells to chemotherapy, but cadm1 knockdown induced chemo-resistance. mechanically, cadm1 interacted with bmi1 to inhibit its nuclear translocation. moreover, mycn which was overexpressed in drug-resistant tc cells directly bound to the mir-21 promoter to upregulated mir-21 expression in tc cells. importantly, the expression levels of mir-21 and cadm1 negatively correlated, but mycn and mir-21 positively correlated in tc tissues. high levels of mir-21 and mycn and low level of cadm1 were associated with poor prognosis in tc patients. in conclusion, our study suggests an important role of the mycn/mir-21/cadm1 axis in chemo-resistance in tc patients and lead to promising prognostic biomarkers and novel treatment strategies to improve the chemotherapeutic efficacy for tc patients.