Abstract 1115: Serum miR152 as a novel prognostic biomarker and potential tumor suppressor for early stage non-small cell lung cancer

Abstract

Abstract Cancer-derived circulating miRNAs represent a promising new class of circulating biomarkers for cancer detection, prognosis, and therapeutic targets. We analyzed the differential c-miRNA expression levels of ∼100 candidate serum miRNAs by quantitative RT-PCR in 174 Caucasian, early stage lung cancer patients and 184 Caucasian healthy controls. Serum miR152 exhibited significant differential expression between cases and controls (P = 0.014). Low levels of serum miR152 expression were consistently associated with an increased risk of lung cancer. The down-regulated miR152 expression was also detected across a panel of 40 NSCLC and normal bronchial epithelial cell lines and in 250 primary tumors by miRNA expression profiling on microarrays. The tumor-derived origin of the c-miR150 was confirmed by an increased level of serum miR152 with increased tumor volumes three weeks after tumor cell inoculation in a human H1299 tumor xenograft mouse model by qRT-PCR assay. Ectopic expression of miR-152 suppressed tumor cell proliferation, colony formation, and cell migration/invasion in NSCLC H1299, H460, and A549 cells transfected by miR-152 expression plasmids. Inhibition of miR-152 expression by a miR-152 inhibitor promoted tumor cell proliferation in HCC15 cells. Overexpression of miR152 in H1299, H460 and A549 cells significantly down-regulated the constitutive expression of the DNMT1 miR-152 target gene and protein, suggesting its potential role in the epigenetic regulation of lung cancer pathogenesis. These results suggest that serum miR-152 may serve as a novel negative predictor for lung cancer risk, recurrence, and survival in early stage NSCLC and function as a potential tumor suppressor miRNA by epigenetic down-regulation of oncogenesis.(This study is partially supported by NIH/NCI grants Lung SPORE 5P50CA070907 and R01CA176568, a CPRIT Grant and a MDACC Moonshot Program Grant) Citation Format: Taro Oba, Yuanqing Ye, Liren Zhang, Jing Lin, Emanuela Gentile, Jing Wang, Yang Zhao, Jiang Gu, Ignacio Wistuba, Jack A. Roth, Xifeng Wu, Lin Ji. Serum miR152 as a novel prognostic biomarker and potential tumor suppressor for early stage non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1115.