Open AccessStathmin1 increases radioresistance by enhancing autophagy in non-small-cell lung cancer cells
Author(s) -
Xi Zhang,
Jingfen Ji,
Yujia Yang,
Juan Zhang,
Liangfang Shen
Publication year - 2016
Publication title -
oncotargets and therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.054
H-Index - 60
ISSN - 1178-6930
DOI - 10.2147/ott.s100468
Subject(s) - radioresistance , autophagy , lung cancer , cancer research , cell , cancer , medicine , biology , pathology , radiation therapy , apoptosis , biochemistry
Radioresistance has been demonstrated to be involved in the poor prognosis of patients with non-small-cell lung cancer (NSCLC). However, the underlying mechanism remains largely unclear. Investigation on special therapeutic targets associated with radioresistance shows promises for the enhancement of clinical radiotherapy effect toward NSCLC. This study aimed to reveal the role of Stathmin1 (STMN1) in radioresistance in NSCLC as well as the underlying mechanism. Our data showed that the protein levels of STMN1 were significantly upregulated in NSCLC cells subjected to radiation, accompanied with the activation of autophagy. Knockdown of STMN1 expression enhanced the sensitivity of NSCLC cells to X-ray, and the radiation-induced autophagy was also inhibited. Molecular mechanism investigation showed that knockdown of STMN1 expression upregulated the activity of phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway in NSCLC cells. Moreover, the activation of PI3K/mTOR signaling showed an inhibitory effect on the autophagy and radioresistance induced by STMN1 in NSCLC cells. In addition, luciferase reporter assay data indicated that STMN1 was a direct target gene of miR-101, which had been reported to be an inhibitor of autophagy. Based on these data, we suggest that as a target gene of miR-101, STMN1 promotes the radioresistance by induction of autophagy through PI3K/mTOR signaling pathway in NSCLC. Therefore, STMN1 may become a potential therapeutic target for NSCLC radiotherapy.