Correlation of long non-coding RNA <i>H19</i> expression with cisplatin-resistance and clinical outcome in lung adenocarcinoma

Abstract

// Qi Wang 1, * , Ningning Cheng 2, * , Xuefei Li 3 , Hui Pan 1 , Chunyu Li 4 , Shengxiang Ren 1 , Chunxia Su 1 , Weijing Cai 1 , Chao Zhao 3 , Limin Zhang 1 , Caicun Zhou 1 1 Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, P.R. China 2 Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 201620, P. R. China 3 Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Tongji University Medical School Cancer Institute, Shanghai, 200433, P.R. China 4 International Medical School, Tianjin Medical University, Tianjin, 300070, P.R. China * These authors contributed equally to this work Correspondence to: Caicun Zhou, email: caicunzhoudr@163.com Keywords: long non-coding RNA, lung adenocarcinoma, H19, cisplatin, A549/DDP cells Received: June 29, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: November 21, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: November 29, 2016 ABSTRACT The acquired drug resistance would influence the efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer. The present study aimed to investigate the correlation of long non-coding RNA (lncRNA) H19 with cisplatin-resistance and clinical outcome in lung adenocarcinoma. In our study, the expression of H19 in cisplatin-resistant A549/DDP cells was unregulated. Knockdown of H19 restored the response of A549/DDP cells to cisplatin. H19 -mediated chemosensitivity enhancement was associated with metastasis, induction of G0/G1 cell-cycle arrest, cell proliferation, and increased apoptosis. Furthermore, lncRNA H19 expression was significantly related to TNM stage and metastasis ( P = 0.012). Overexpression of H19 was negatively correlated with cisplatin-based chemotherapy response in patients. Patients with high H19 expression exhibited a significantly shorter median progression-free survival (PFS) [4.7 months] than the low-expression patients (6.3months) [ P = 0.002]. In summary, H19 -mediated regulation of cisplatin resistance in human lung adenocarcinoma cells is demonstrated for the first time. H19 could potentially serve as a molecular marker to predict the clinical outcomes of lung adenocarcinoma patients.