title: The down-regulated ING5 expression in lung cancer: a potential target of gene therapy.
abstract: ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. We found that ING5 overexpression not only inhibited proliferation, migration, and invasion, but also induced G2 arrest, differentiation, autophagy, apoptosis, glycolysis and mitochondrial respiration in lung cancer cells. ING5 transfection up-regulated the expression of Cdc2, ATG13, ATG14, Beclin-1, LC-3B, AIF, cytochrome c, Akt1/2/3, ADFP, PFK-1 and PDPc, while down-regulated the expression of Bcl-2, XIAP, survivin,β-catenin and HXK1. ING5 transfection desensitized cells to the chemotherapy of MG132, paclitaxel, and SAHA, which paralleled with apoptotic alteration. ING5 overexpression suppressed the xenograft tumor growth by inhibiting proliferation and inducing apoptosis. ING5 expression level was significantly higher in normal tissue than that in lung cancer at both protein and mRNA levels. Nuclear ING5 expression was positively correlated with ki-67 expression and cytoplasmic ING5 expression. Cytoplasmic ING5 expression was positively associated with lymph node metastasis, and negatively with age, lymphatic invasion or CPP32 expression. ING5 expression was different in histological classification: squamous cell carcinoma > adenocarcinoma > large cell carcinoma > small cell carcinoma. Taken together, our data suggested that ING5 downregulation might involved in carcinogenesis, growth, and invasion of lung cancer and could be considered as a promising marker to gauge the aggressiveness of lung cancer. It might be employed as a potential target for gene therapy of lung cancer.
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Dao-Fu
authors.initials: DF
authors.lastname: Shen
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Shi
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Hong-Xu
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Sun
authors.affiliation: Life Science Institute of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Rong-Jian
authors.initials: RJ
authors.lastname: Su
authors.affiliation: Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.|Life Science Institute of Jinzhou Medical University, Jinzhou, 121001, China.
authors.forename: Hua-Chuan
authors.initials: HC
authors.lastname: Zheng
mesh_terms: D000072283:A549 Cells; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053208:Kaplan-Meier Estimate; D007976:Leupeptins / Q000494:pharmacology; D008175:Lung Neoplasms / Q000145:classification / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D017239:Paclitaxel / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D000077337:Vorinostat; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; C508131:ING5 protein, human; D007976:Leupeptins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000077337:Vorinostat; D017239:Paclitaxel; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: ING5; aggressiveness; lung cancer; pathogenesis; prognosis