Downregulation of LNMAS orchestrates partial EMT and immune escape from macrophage phagocytosis to promote lymph node metastasis of cervical cancer.
Downregulation of LNMAS orchestrates partial EMT and immune escape from macrophage phagocytosis to promote lymph node metastasis of cervical cancer.
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LNMAS下调协调部分EMT和巨噬细胞吞噬的免疫逃逸促进宫颈癌淋巴结转移
DOI：
10.1038/s41388-022-02202-3
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发表时间：
2022-03
期刊：
影响因子：
8
通讯作者：
Yao S
中科院分区：
文献类型：
--
作者：
Liao Y;Huang J;Liu P;Zhang C;Liu J;Xia M;Shang C;Ooi S;Chen Y;Qin S;Du Q;Liu T;Xu M;Zou Q;Zhou Y;Huang H;Pan Y;Wang W;Yao S
上皮-间充质转化(EMT)是推动宫颈癌细胞向淋巴结(LNS)转移的重要步骤。然而，很少有转移成功，部分原因是EMT增加了对免疫监视的敏感性。癌细胞协调EMT和免疫逃避的确切机制在很大程度上仍未被探索。在本研究中，我们发现了一种被称为淋巴转移相关抑制因子(LNMAS)的LncRNA，它在LN阳性的宫颈癌患者中表达下调，并与LN转移和预后相关。从功能上讲，LNMAS在体内外均能抑制宫颈癌细胞的转移。在机制上，LNMAS通过竞争性地与HMGB1相互作用，取消Twist1和STc1的染色质可及性，抑制Twist1介导的部分EMT和STc1依赖的免疫逃逸巨噬细胞吞噬功能，从而发挥其肿瘤转移抑制活性。我们进一步证明了LNMAS基因启动子区域的CpG位点发生了高甲基化，并参与了LNMAS基因的下调。综上所述，我们的结果揭示了LNMAS在宫颈癌LN转移中的重要作用，并为LNMAS在EMT和免疫逃避中的调控提供了机制方面的见解。
Epithelial-mesenchymal transition (EMT) is an essential step to drive the metastatic cascade to lymph nodes (LNs) in cervical cancer cells. However, few of them metastasize successfully partially due to increased susceptibility to immunosurveillance conferred by EMT. The precise mechanisms of cancer cells orchestrate EMT and immune evasion remain largely unexplored. In this study, we identified a lncRNA termed lymph node metastasis associated suppressor (LNMAS), which was downregulated in LN-positive cervical cancer patients and correlated with LN metastasis and prognosis. Functionally, LNMAS suppressed cervical cancer cells metastasis in vitro and in vivo. Mechanistically, LNMAS exerts its metastasis suppressive activity by competitively interacting with HMGB1 and abrogating the chromatin accessibility of TWIST1 and STC1, inhibiting TWIST1-mediated partial EMT and STC1-dependent immune escape from macrophage phagocytosis. We further demonstrated that the CpG sites in the promoter region of LNMAS was hypermethylated and contributed to the downregulation of LNMAS. Taken together, our results reveal the essential role of LNMAS in the LN metastasis of cervical cancer and provide mechanistic insights into the regulation of LNMAS in EMT and immune evasion.
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影响因子：
5.6
作者：
Blair RH;Horn AE;Pazhani Y;Grado L;Goodrich JA;Kugel JF
通讯作者：
Kugel JF
影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
影响因子：
10.6
作者：
Kang, Rui;Chen, Ruochan;Zhang, Qiuhong;Hou, Wen;Wu, Sha;Cao, Lizhi;Huang, Jin;Yu, Yan;Fan, Xue-gong;Yan, Zhengwen;Sun, Xiaofang;Wang, Haichao;Wang, Qingde;Tsung, Allan;Billiar, Timothy R.;Zeh, Herbert J., III;Lotze, Michael T.;Tang, Daolin
通讯作者：
Tang, Daolin
影响因子：
15.9
作者：
Chockley, Peter J.;Chen, Jun;Keshamouni, Venkateshwar G.
通讯作者：
Keshamouni, Venkateshwar G.
DOI：
10.1097/igc.0b013e3182778bcf
发表时间：
2013-01-01
影响因子：
4.8
作者：
Chen, Ying;Zhang, Lei;Hao, Quan
通讯作者：
Hao, Quan