机构：[1]Department of Urology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou, Guangdong, China临床科室其他部门泌尿外科华南肿瘤学国家重点实验室中山大学肿瘤防治中心
The prognosis for bladder cancer patients with lymph node (LN) metastasis is dismal and only minimally improved by current treatment modalities. Elucidation of the molecular mechanisms that underlie LN metastasis May provide clinical therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a long noncoding RNA LINC00958, which we have termed bladder cancer–associated transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer and correlated with LN metastasis. Overexpression of BLACAT2 promoted bladder cancer–associated lymphangiogenesis and lymphatic metastasis in both cultured bladder cancer cell lines and mouse models. Furthermore, we demonstrate that BLACAT2 epigenetically upregulated VEGF-C expression by directly associating with WDR5, a core subunit of human H3K4 methyltransferase complexes. Importantly, administration of an anti–VEGF-C antibody inhibited LN metastasis in BLACAT2-overexpressing bladder cancer. Taken together, these findings uncover a molecular mechanism in the lymphatic metastasis of bladder cancer and indicate that BLACAT2 May represent a target for clinical intervention in LN-metastatic bladder cancer.
基金：
This study was funded by the National Natural Science Foundation of China (Grant No. 81572514, 81472384, 81472381, 81402106, 81772719, 81772728, 91740119); Guangdong Science and Technology Development Fund (2017B020227007); Science and Technology Program of Guangzhou (Grant No. 201604020156, 201604020177, 201707010116); National Natural Science Foundation of Guangdong (Grant No. 2016A030313321, 2015A030311011, 2015A030310122, 2014A030310133, S2013020012671, 07117336, 10151008901000024), “Three Big Constructions” funds of Sun Yat-sen University; Project Supported by Guangdong Province Higher Vocational Colleges & Schools Pearl River Scholar Funded Scheme; Elite Young Scholars Program of Sun Yat-Sen Memorial Hospital (J201401, J2015-106); Fundamental Research Funds for Young Teachers in the Higher Education Institutions of China (16ykpy12); National Clinical Key Specialty Construction Project for Department of Urology and Department of Oncology. The Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun-Yat-Sen University (Grant KLB09001); Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology ([2013]163).
第一作者机构：[1]Department of Urology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou, Guangdong, China
推荐引用方式(GB/T 7714)：
He W,Zhong G,Jiang N,et al.Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis[J].Journal of Clinical Investigation.2018,128(2):doi:10.1172/JCI96218.
APA：
He, W,Zhong, G,Jiang, N,Wang, B,Fan, X...&Lin, T.(2018).Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis.Journal of Clinical Investigation,128,(2)
MLA：
He, W,et al."Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis".Journal of Clinical Investigation 128..2(2018)
医学