title: PIG3 promotes NSCLC cell mitotic progression and is associated with poor prognosis of NSCLC patients.
abstract: Non-small cell lung cancer (NSCLC) is the most commonly diagnosed type of lung cancer that is associated with poor prognosis. In this study we explored the potential role of p53-induced gene 3 (PIG3) in the progression of NSCLC.
  
  
  
  Immunohistochemistry was used to determine the expression levels of PIG3 in 201 NSCLC patients. We performed in vitro studies and silenced endogenous PIG3 by using specific siRNAs that specific target PIG3. Immunofluorescent staining was performed to determine the effect of PIG3 on mitotic progression in NSCLC cells. The growth rates of microtubules were determined by microtubule nucleation analysis. Cell proliferation and chemosensitivity were analyzed by CCK8 assays. Annexin V staining and β-galactosidase activity analysis were used to evaluate PIG3 deficiency-related apoptosis and senescence, respectively.
  
  
  
  PIG3 expression levels negatively correlated with overall survival and disease-free survival of NSCLC patients. Knock down of PIG3 resulted in repressed proliferation of NSCLC cells and increased aberrant mitosis, which included misaligning and lagging chromosomes, and bi- or multi-nucleated giant cells. In addition, PIG3 contributed to mitotic spindle assembly by promoting microtubule growth. Furthermore, loss of PIG3 sensitized NSCLC cells to docetaxel by enhancing docetaxel-induced apoptosis and senescence.
  
  
  
  Our results indicate that PIG3 promotes NSCLC progression and therefore suggest that PIG3 may be a potential prognostic biomarker and novel therapeutic target for the treatment of NSCLC.
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu, 215123, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, 100850, People's Republic of China.
authors.forename: Shanhu
authors.initials: S
authors.lastname: Li
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, People's Republic of China.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu, 215123, People's Republic of China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Gu
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, People's Republic of China.
authors.forename: Shitao
authors.initials: S
authors.lastname: Zou
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu, 215123, People's Republic of China.
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Xiao
authors.affiliation: Department of Radiation Oncology, Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, 75390, TX, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK, 73104, USA.
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Ding
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, 100850, People's Republic of China.
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, People's Republic of China. zhoujundong330@163.com.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu, 215123, People's Republic of China. ziyu_620@163.com.|Department of Radiation Oncology, Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, 75390, TX, USA. ziyu_620@163.com.
authors.forename: Zeng-Fu
authors.initials: ZF
authors.lastname: Shang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008938:Mitosis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis; D043823:Taxoids / Q000494:pharmacology; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; C411296:TP53I3 protein, human; D043823:Taxoids; D000077143:Docetaxel
keywords: Chemoresistance; Microtubule assembly; Mitotic progression; Non-small cell lung cancer (NSCLC); p53-induced gene 3 (PIG3)