Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 497, Issue 4, Pages 1003-1010Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.02.141
Keywords
HOTAIR; Drug resistance; NSCLC; Autophagy; ULK1
Categories
Ask authors/readers for more resources
Drug resistance is an important factor leading to the recurrence and metastasis of Non-Small Cell Lung Cancer (NSCLC). Long non-coding RNAs (LncRNAs) play important roles in drug resistance of tumor cells. The aim of our study was to investigate the mechanism of LncRNA-HOTAIR in regulating drug resistance of NSCLC cells. Our data indicated that HOTAIR was overexpressed in NSCLC cell lines. Silencing of HOTAIR decreased cell proliferation and increased apoptosis of NSCLC cells (A549). Besides that, HOTAIR shRNA transfection suppressed drug resistance of A549 cells to Crizotinib by more effectively inhibiting cell viability and promoting apoptosis compared with HOTAIR scramble group. Moreover, silencing of HOTAIR decreased the number of LC3(+) puncta and the expression of Beclinl, p-ULK1 and the ratio of LO II/I/in Crizotinib treated A549 cells, indicating that silencing of HOTAIR decreased drug resistance of NSCLC cells might through inhibiting autophagy via the ULK1 pathway. In order to further prove our conclusion, Rapamycin (Rapa), an autophagy inducer, was used in our study. With the adjunction of Rapa, obvious autophagy was induced by increasing the number of LC3(+) puncta, the ratio of LO III and the expression of p-ULK1 compared with Crizotinib + HOTAIR shRNA group. What is more, the activation of autophagy abolished the effect of HOTAIR shRNA on decreasing drug resistance by increasing cell viability and decreasing cell apoptosis. These results supported our conclusion that silencing of HOTAIR decreased drug resistance of NSCLC cells to Crizotinib through inhibition of autophagy via suppressing phosphorylation of ULK1. (C) 2018 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available