BRAF-activated LncRNA functions as a tumor suppressor in papillary thyroid cancer

Abstract

// Tian Liao 1, * , Ning Qu 1, * , Rong-Liang Shi 1, 2, * , Kai Guo 1 , Ben Ma 1 , Yi-Ming Cao 1 , Jun Xiang 1 , Zhong-Wu Lu 1 , Yong-Xue Zhu 1 , Duan-Shu Li 1 , Qing-Hai Ji 1 1 Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China 2 Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, China * These authors contributed equally to this work Correspondence to: Qing-Hai JI, email: jiqinghai@shca.org.cn Keywords: papillary thyroid cancer, BRAF, lncRNA, proliferation, migration Received: November 30, 2015      Accepted: June 06, 2016      Published: July 24, 2016 ABSTRACT Long non-coding RNAs (lncRNAs) participate in cancer cell tumorigenesis, cell cycle control, migration, proliferation, apoptosis, metastasis and drug resistance. The BRAF-activated non-coding RNA (BANCR) functions as both an oncogene and a tumor suppressor. Here, we investigated BANCR’s role in papillary thyroid carcinoma (PTC) by assessing BANCR levels in PTC and matched normal thyroid epithelial tissues from 92 patients using qRT-PCR. We also used lentiviral vectors to establish PTC cell lines to investigate the effects of BANCR overexpression on cancer cell proliferation, apoptosis, migration and invasion. Our results indicate BANCR levels are lower in PTC tumor tissues than control tissues. Decreased BANCR levels correlate with tumor size, the presence of multifocal lesions and advanced PTC stage. BANCR overexpression reduced PTC cell proliferation and promoted apoptosis, which inhibited metastasis. It also inactivated ERK1/2 and p38, and this effect was enhanced by treatment with the MEK inhibitor U0126. Finally, BANCR overexpression dramatically inhibited tumor growth from PTC cells in xenograft mouse models. These results suggest BANCR inhibits tumorigenesis in PTC and that BANCR levels may be used as a novel prognostic marker.