TNFAIP8 promotes the proliferation and cisplatin chemoresistance of non-small cell lung cancer through MDM2/p53 pathway

• DOI: 10.1186/s12964-018-0254-x
• Publication Date: 2018-07-31T13:00:17Z
• Authors: Ying Xing; Yuechao Liu; Tianbo Liu; Qingwei Meng; Hailing Lu; Wei Liu; Jing Hu; Chunhong Li; Mengru Cao; Shi Yan; Jian Huang; Ting Wang; Li Cai
• Keywords: Male; 0301 basic medicine; Lung Neoplasms; TNFAIP8; Proliferation; Cisplatin chemoresistance; NSCLC; Mice; 03 medical and health sciences; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Animals; Humans; Cell Proliferation; 2. Zero hunger; QH573-671; Research; Cell Cycle; R; MDM2/p53 pathway; Proto-Oncogene Proteins c-mdm2; Middle Aged; Xenograft Model Antitumor Assays; 3. Good health; Gene Expression Regulation, Neoplastic; Drug Resistance, Neoplasm; Medicine; Female; Cisplatin; Tumor Suppressor Protein p53; Cytology; Apoptosis Regulatory Proteins; Signal Transduction

The highly refractory nature of non-small cell lung cancer (NSCLC) to chemotherapeutic drugs is an important factor resulting in its poor prognosis. Recent studies have revealed that tumour necrosis alpha-induced protein 8 (TNFAIP8) involved various biological and pathological processes cells, but their underlying mechanisms ranging from development drug resistance not been fully elucidated. TNFAIP8 expression clinical NSCLC samples was examined through immunohistochemistry (IHC). After adjusting for patients' characteristics with propensity score matching, Kaplan-Meier analysis Cox regression were performed comparison survival according the level. Lentiviral transfection TNFAIP8-specific shRNAs used establish stable knockdown (TNFAIP8 KD) NCI-H460, A549 cis-diamminedichloroplatinum II resistant (A549/cDDP) lines. Cell proliferation viability assessed by CCK-8 assay. cycle flow cytometry. Multiple pathways regulated KD microarray analysis. We found high associated advanced pT stage, pTNM lymph node metastasis unfavourable patients. reduced vitro vivo tumor growth. Additionally, increased sensitivity cells cisplatin vivo. Conversely, up-regulation promoted cells. influences progression involving MDM2/p53 pathway. Indeed, we observed mediated MDM2 downregulation p53 ubiquitination, thereby decreasing degradation protein. shRNA reversed shRNA-mediated regulation proliferation, cycle, sensitivity, levels RAD51, a DNA repair gene. Our work uncovers hitherto unappreciated role chemoresistance These findings might offer potential therapeutic targets reversing patients expression.