The down-regulated ING5 expression in lung cancer: A potential target of gene therapy

// Shuang Zhao 1 , Xue-feng Yang 1 , Dao-fu Shen 1 , Yang Gao 1 , Shuai Shi 1 , Ji-cheng Wu 1 , Hong-xu Liu 2 , Hong-zhi Sun 1 , Rong-jian Su 3 , Hua-chuan Zheng 1, 3 1 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 2 Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China 3 Life Science Institute of Jinzhou Medical University, Jinzhou, 121001, China Correspondence to: Hua-chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: lung cancer, ING5, pathogenesis, aggressiveness, prognosis Received: February 06, 2016      Accepted: May 28, 2016      Published: July 09, 2016 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.