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BRAF激活的长链非编码RNA在甲状腺乳头状癌中发挥肿瘤抑制作用。

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

作者信息

Liao Tian, Qu Ning, Shi Rong-Liang, Guo Kai, Ma Ben, Cao Yi-Ming, Xiang Jun, Lu Zhong-Wu, Zhu Yong-Xue, Li Duan-Shu, Ji Qing-Hai

机构信息

Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Department of General Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, China.

出版信息

Oncotarget. 2017 Jan 3;8(1):238-247. doi: 10.18632/oncotarget.10825.

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.

摘要

长链非编码RNA(lncRNAs)参与癌细胞的肿瘤发生、细胞周期调控、迁移、增殖、凋亡、转移及耐药性。BRAF激活的非编码RNA(BANCR)兼具癌基因和肿瘤抑制基因的功能。在此,我们通过qRT-PCR检测92例患者甲状腺乳头状癌(PTC)组织及配对的正常甲状腺上皮组织中BANCR的水平,研究BANCR在PTC中的作用。我们还利用慢病毒载体构建PTC细胞系,以研究BANCR过表达对癌细胞增殖、凋亡、迁移及侵袭的影响。我们的结果表明,PTC肿瘤组织中BANCR水平低于对照组织。BANCR水平降低与肿瘤大小、多灶性病变的存在及PTC晚期相关。BANCR过表达可降低PTC细胞增殖并促进凋亡,从而抑制转移。它还可使ERK1/2和p38失活,MEK抑制剂U0126处理可增强这种作用。最后,BANCR过表达显著抑制了异种移植小鼠模型中PTC细胞的肿瘤生长。这些结果提示BANCR可抑制PTC肿瘤发生,且BANCR水平可能用作一种新的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/606a/5352115/7d3b1766eea5/oncotarget-08-238-g001.jpg

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