Zhao Shuang, Yang Xue-Feng, Shen Dao-Fu, Gao Yang, Shi Shuai, Wu Ji-Cheng, Liu Hong-Xu, Sun Hong-Zhi, Su Rong-Jian, Zheng Hua-Chuan
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.
Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
Oncotarget. 2016 Aug 23;7(34):54596-54615. doi: 10.18632/oncotarget.10519.
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.
ING5可与p53相互作用，从而抑制细胞生长并诱导细胞凋亡。我们发现，ING5过表达不仅抑制肺癌细胞的增殖、迁移和侵袭，还诱导其G2期阻滞、分化、自噬、凋亡、糖酵解和线粒体呼吸。ING5转染上调了Cdc2、ATG13、ATG14、Beclin-1、LC-3B、AIF、细胞色素c、Akt1/2/3、ADFP、PFK-1和PDPc的表达，同时下调了Bcl-2、XIAP、survivin、β-连环蛋白和HXK1的表达。ING5转染使细胞对MG132、紫杉醇和SAHA的化疗产生脱敏作用，这与凋亡改变平行。ING5过表达通过抑制增殖和诱导凋亡来抑制异种移植肿瘤的生长。在蛋白质和mRNA水平上，ING5在正常组织中的表达水平均显著高于肺癌组织。核ING5表达与ki-67表达呈正相关，胞质ING5表达与ki-67表达也呈正相关。胞质ING5表达与淋巴结转移呈正相关，与年龄、淋巴管浸润或CPP32表达呈负相关。ING5在组织学分类中的表达存在差异：鳞状细胞癌>腺癌>大细胞癌>小细胞癌。综上所述，我们的数据表明，ING5下调可能参与肺癌的发生、生长和侵袭，可被视为评估肺癌侵袭性的一个有前景的标志物。它可能被用作肺癌基因治疗的潜在靶点。
