title: Stathmin1 increases radioresistance by enhancing autophagy in non-small-cell lung cancer cells.
abstract: 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.
authors.affiliation: Department of Oncology, Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China; Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Jingfen
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Oncology, 163 Hospital of PLA, Changsha, Hunan, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Xiangya Hospital of Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Shen
keywords: PI3K; STMN1; autophagy; mTOR pathway; non-small-cell lung cancer; radioresistance