title: Downregulation of ribosomal protein S6 inhibits the growth of non-small cell lung cancer by inducing cell cycle arrest, rather than apoptosis.
abstract: Ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit, has been found to be associated with multiple physiological and pathophysiological functions. However, its effects and mechanisms in non-small cell lung cancer (NSCLC) still remain unknown. Here, we showed that expressions of total rpS6 and phosphorylation rpS6 (p-rpS6) were both significantly overexpressed in NSCLC. Further survival analysis revealed the shortened overall survival (OS) and relapse-free survival (RFS) in p-rpS6 overexpressed patients and confirmed it as an independent adverse predictor. Stable downregulation of rpS6 in lung adenocarcinoma A549 and squamous cell carcinoma H520 cell lines was then achieved by two specific small hairpin RNA (shRNA) lentiviruses separately. Subsequent experiments showed that downregulation of rpS6 dramatically inhibited cell proliferation in vitro and tumorigenicity in vivo. Moreover, loss of rpS6 promoted cells arrested in G0-G1 phase and reduced in G2-M phase, along with the expression alterations of relative proteins. However, no notable change in apoptosis was observed. Collectively, these results suggested that rpS6 is overactivated in NSCLC and its downregulation suppresses the growth of NSCLC mainly by inducing G0-G1 cell cycle arrest rather than apoptosis.
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China; State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Bojiang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China; Department of Respiratory Medicine, Second Affiliated Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Toxicological Inspection, Sichuan Center for Disease Prevention and Control, Chengdu, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Geriatric Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China; Department of Respiratory Medicine, Second Clinical Medical School, North Sichuan Medical College (Nanchong Central Hospital, Sichuan), Nanchong, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Shangfu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, China; State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China. Electronic address: weimi003@yahoo.com.
authors.forename: Weimin
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D038601:Ribosomal Protein S6 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D038601:Ribosomal Protein S6
keywords: Apoptosis; Cell cycle; Growth; Non-small cell lung cancer (NSCLC); Ribosomal protein S6 (rpS6)