MiR-381-3p attenuates doxorubicin resistance in human anaplastic thyroid carcinoma via targeting homeobox A9.

Abstract

Abnormal microRNA (miR) expression has frequently been reported to be implicated in cancer-related drug resistance. Herein, we planned to investigate whether miR-381-3p contributes to doxorubicin (DOX) resistance in anaplastic thyroid carcinoma (ATC). DOX-resistant ATC tissues and cell lines were prepared to detect miR-381-3p and homeobox A9 (HOXA9) expression. CCK8, transwell and TUNEL assays were performed to evaluate cell proliferation, migration and invasion, and apoptosis in in vitro experiments. HOXA9 expression is intensively expressed in ATC tissues compared with benign thyroid tissues. Compared with parental ATC cell lines, HOXA9 protein expression is significantly up-regulated in DOX-resistant SW1736 and CAL62 cells. The knockdown of HOXA9 leads to growth inhibition and apoptosis of DOX-resistant SW1736 and CAL62 cells. Our results also indicate a significant decrease in miR-381-3p expression levels in DOX-resistant ATC tissues and cell lines. miR-381-3p may function as a tumour suppressor to impede proliferation, migration and invasion and induce apoptosis of DOX-resistant SW1736 and CAL62 cells by inhibiting HOXA9 protein expression. Our results present a novel signalling axis miR-381-3p/HOXA9 that mediates DOX resistance in ATC. miR-381-3p and HOXA9 may be promising molecular targets for preventing ATC progression and drug resistance.