LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment.
LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment.
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LNMAT1 通过 CCL2 依赖性巨噬细胞募集促进膀胱癌淋巴转移
DOI：
10.1038/s41467-018-06152-x
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发表时间：
2018-09-20
影响因子：
16.6
通讯作者：
Lin T
中科院分区：
文献类型：
--
作者：
Chen C;He W;Huang J;Wang B;Li H;Cai Q;Su F;Bi J;Liu H;Zhang B;Jiang N;Zhong G;Zhao Y;Dong W;Lin T
肿瘤相关巨噬细胞（Tumor-associated macrophages，TAM）是肿瘤微环境中最丰富的炎性浸润细胞，参与淋巴结（lymph node，LN）转移。然而，TAMs诱导LN转移的确切机制仍不清楚。在此，我们鉴定了一个长的非编码RNA，称为淋巴结转移相关转录1（LNMAT 1），它在LN阳性膀胱癌中上调，并与LN转移和预后相关.通过功能获得和丧失的研究，我们发现LNMAT 1促进膀胱癌相关的淋巴管生成和淋巴转移。在机制上，LNMAT 1通过募集hnRNPL到CCL 2启动子，导致H3 K4三甲基化增加，从而确保hnRNPL结合并增强转录，从而表观遗传学激活CCL 2表达.此外，LNMAT 1诱导的CCL 2上调募集巨噬细胞进入肿瘤，这通过VEGF-C分泌促进淋巴转移。这些发现为LNMAT 1调节淋巴转移的肿瘤微环境提供了一个合理的机制，并提示LNMAT 1可能是临床干预淋巴转移性膀胱癌的一个潜在治疗靶点。肿瘤相关巨噬细胞（tumor associated macrophages，TAMs）诱导淋巴结（lymph node，LN）转移的机制尚不清楚。在这里，他们证明了一个长的非编码RNA LNMAT 1促进膀胱癌的LN转移通过招募TAM通过表观遗传调节CCL 2的表达。
Tumor-associated macrophages (TAMs) are the most abundant inflammatory infiltrates in the tumor microenvironment and contribute to lymph node (LN) metastasis. However, the precise mechanisms of TAMs-induced LN metastasis remain largely unknown. Herein, we identify a long noncoding RNA, termed Lymph Node Metastasis Associated Transcript 1 (LNMAT1), which is upregulated in LN-positive bladder cancer and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that LNMAT1 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, LNMAT1 epigenetically activates CCL2 expression by recruiting hnRNPL to CCL2 promoter, which leads to increased H3K4 tri-methylation that ensures hnRNPL binding and enhances transcription. Furthermore, LNMAT1-induced upregulation of CCL2 recruits macrophages into the tumor, which promotes lymphatic metastasis via VEGF-C excretion. These findings provide a plausible mechanism for LNMAT1-modulated tumor microenvironment in lymphatic metastasis and suggest that LNMAT1 may represent a potential therapeutic target for clinical intervention in LN-metastatic bladder cancer. Mechanism of lymph node (LN) metastasis induced by tumor associated macrophages (TAMs) remains unclear. Here they demonstrate that a long noncoding RNA LNMAT1 promotes LN metastasis of bladder cancer via recruitment of TAMs through epigenetic regulation of CCL2 expression.
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DOI：
10.1007/978-1-4939-6380-5_10
发表时间：
2016-01-01
期刊：
POLYCOMB GROUP PROTEINS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Chu, Ci;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
6.4
作者：
Maniecki, Maciej Bogdan;Etzerodt, Anders;Moller, Holger Jon
通讯作者：
Moller, Holger Jon
影响因子：
16.6
作者：
Ji, Hong;Cao, Renhai;Cao, Yihai
通讯作者：
Cao, Yihai
影响因子：
5.8
作者：
He, Sha;Zhang, Hai;Zhu, Hao
通讯作者：
Zhu, Hao
影响因子：
14.9
作者：
Kalwa M;Hänzelmann S;Otto S;Kuo CC;Franzen J;Joussen S;Fernandez-Rebollo E;Rath B;Koch C;Hofmann A;Lee SH;Teschendorff AE;Denecke B;Lin Q;Widschwendter M;Weinhold E;Costa IG;Wagner W
通讯作者：
Wagner W