The down-regulated ING5 expression in lung cancer: A potential target of gene therapy
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Shuang Zhao1, Xue-feng Yang1, Dao-fu Shen1, Yang Gao1, Shuai Shi1, Ji-cheng Wu1, Hong-xu Liu2, Hong-zhi Sun1, Rong-jian Su3, Hua-chuan Zheng1,3
1Cancer 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
2Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China
3Life Science Institute of Jinzhou Medical University, Jinzhou, 121001, China
Hua-chuan Zheng, email: [email protected]
Keywords: lung cancer, ING5, pathogenesis, aggressiveness, prognosis
Received: February 06, 2016 Accepted: May 28, 2016 Published: July 09, 2016
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.
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