Shen Bo, Yuan Yuan, Zhang Yan, Yu Shaorong, Peng Wei, Huang Xin'en, Feng Jifeng
Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 42 Baiziting, Nanjing, Jiangsu Province 210009, China.
Department of Oncology, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, 42 Baiziting, Nanjing, Jiangsu Province 210009, China.
Biochem Biophys Res Commun. 2017 Jun 17;488(1):67-73. doi: 10.1016/j.bbrc.2017.05.008. Epub 2017 May 4.
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the progression of human cancers, including colorectal cancer (CRC). The study of genome-wide lncRNA expression patterns in metastatic CRC could provide novel mechanism underlying CRC carcinogenesis. In here, we determined the lncRNA expression profiles correlating to CRC with or without lymph node metastasis (LNM) based on microarray analysis. We found that 2439 lncRNAs and 1654 mRNAs were differentially expressed in metastatic CRC relative to primary CRC. Among these dysregulated lncRNAs, FBXL19-AS1 was the most significantly upregulated lncRNA in metastatic tumors. Functionally, knockdown of FBXL19-AS1 played tumor-suppressive effects by inhibiting cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Overexpression of FBXL19-AS1 was markedly correlated with TNM stage and LNM in CRC. Bioinformatics analysis predicted that miR-203 was potentially targeted by FBXL19-AS1, which was confirmed by dual-luciferase reporter assay. Pearson's correlation analysis showed that miR-203 expression was negatively related to FBXL19-AS1 in tumor tissues. Finally, miR-203 inhibition abrogated the effect of FBXL19-AS1 knockdown on the proliferation and invasion of LoVo cells. Our results reveal the cancer-promoting effect of FBXL19-AS1, acting as a molecular sponge in negatively modulating miR-203, which might provide a new insight for understanding of CRC development.
长链非编码RNA(lncRNAs)已成为人类癌症进展的关键调节因子,包括结直肠癌(CRC)。对转移性结直肠癌全基因组lncRNA表达模式的研究可为结直肠癌致癌作用提供新的机制。在此,我们基于微阵列分析确定了与有无淋巴结转移(LNM)的结直肠癌相关的lncRNA表达谱。我们发现,相对于原发性结直肠癌,2439个lncRNAs和1654个mRNAs在转移性结直肠癌中差异表达。在这些失调的lncRNAs中,FBXL19-AS1是转移性肿瘤中上调最显著的lncRNA。在功能上,敲低FBXL19-AS1通过在体外抑制细胞增殖、迁移和侵袭以及在体内抑制肿瘤生长和转移发挥肿瘤抑制作用。FBXL19-AS1的过表达与结直肠癌的TNM分期和LNM显著相关。生物信息学分析预测miR-203可能是FBXL19-AS1的靶点,双荧光素酶报告基因检测证实了这一点。Pearson相关性分析表明,肿瘤组织中miR-203表达与FBXL19-AS1呈负相关。最后,抑制miR-203可消除FBXL19-AS1敲低对LoVo细胞增殖和侵袭的影响。我们的结果揭示了FBXL19-AS1作为分子海绵负向调节miR-203从而促进癌症的作用,这可能为理解结直肠癌的发展提供新的见解。