Overexpression of microRNA-145 inhibits tumorigenesis through autophagy in chemotherapy and radiation resistant neuroblastoma cells
Kwang Woon Kim1, Jingbo Qiao1, Julia Y. Kim1, Kyungho Park1, Dai H. Chung1,
1 Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
Dai H. Chung, email:email@example.com
Keywords: chemotherapy; radiotherapy; microRNA-145; LC3 I&II; neuroblastoma
Received: October 04, 2019 Accepted: November 22, 2019 Published: February 01, 2020
MicroRNA-145 (miR-145) plays a suppressive role in the process of tumorigenesis and an important role in induction of autophagy. However, the exact role of miR-145 in therapeutically resistant neuroblastoma cells remain elusive. Herein, we sought to evaluate the effects of miR-145 overexpression in chemo- and radiation-resistant neuroblastoma cells. We hypothesized that miR-145 affects the aggressiveness of resistant cells by enhancing autophagy. We established Cisplatin-resistant (CDDP-R), Vincristine-resistant (Vin-R), and radiation-resistant (Rad-R) neuroblastoma cells and found that miR-145 expression was significantly decreased in the resistant cells compared to the parental cells. Exogenously expression of miR-145 inhibited oncogenic properties such as proliferation, clonogenicity, anchorage-independent growth, cell migration, and tubule formation in the resistant cells. In addition, we also found that an autophagy protein marker, LC3, was only minimally expressed in the resistant cells. In particular, when miR-145 was overexpressed in the resistant cells, LC3 I and II were expressed and an increased punctate fluorescence of LC3 protein was found indicating the induction of autophagy. Taken together, our data suggests that miR-145 inhibits tumorigenesis and aggressiveness via modulation of autophagy in neuroblastoma.