title: SIRT3 is correlated with the malignancy of non-small cell lung cancer.
abstract: The mitochondrial deacetylase SIRT3 plays a pivotal role in the initiation and the progression of certain cancers acting as an oncogene. However, in others it acts anti-oncogenically. Its conflicting action is possibly due to the different key proteins it modifies depending on the context of active intracellular signaling pathways in different cancers. SIRT3 is thus a novel target for preventing and treating cancer. In the present study, we explored the function of SIRT3 in non-small cell lung cancer (NSCLC) with the aim of elucidating the underlying mechanisms. We first determined the SIRT3 expression levels by real-time PCR, western blotting and immunohistochemistry on tissue microarrays of paired samples of NSCLC tissue and adjacent normal tissue from 70 patients with associated clinicopathological data. Levels of SIRT3 protein and mRNA were significantly increased in NSCLC tissue, compared with normal tissue (P<0.05). Expression of SIRT3 in NSCLC positively correlated with that of malignant biomarker Ki-67 (P<0.05) and oncogene p-Akt (P<0.05). Patients with higher SIRT3 expression had a shorter overall survival duration (P<0.05). NSCLC tissue of squamous cell carcinoma type had higher SIRT3 expression compared with other types (P<0.05). Furthermore, among the clinicopathological variables examined, SIRT3 expression was correlated only with pathological type (P<0.05). In NSCLC cell lines, we found that downregulation of SIRT3 by siRNA decreased the activation of Akt, and that SIRT3 overexpression caused the activation of Akt. In addition, in a NSCLC cell line, SIRT3 was able to co-immunoprecipitate Akt and co-located with Akt, suggesting that SIRT3 regulates the activation of Akt through post-transcriptional modification. Our findings suggest that SIRT3 promotes the malignancy of NSCLC, showing an oncogenic preference towards squamous cell carcinoma, and that could represent a novel target for treatment.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Yanlu
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; C466093:SIRT3 protein, human; D056566:Sirtuin 3