Long noncoding RNA lncGALM increases risk of liver metastasis in gallbladder cancer through facilitating N-cadherin and IL-1β-dependent liver arrest and tumor extravasation.
Long noncoding RNA lncGALM increases risk of liver metastasis in gallbladder cancer through facilitating N-cadherin and IL-1β-dependent liver arrest and tumor extravasation.
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长非编码 RNA lncGALM 通过促进 N-钙粘蛋白和 IL-1β 依赖性肝停滞和肿瘤外渗增加胆囊癌肝转移的风险
DOI：
10.1002/ctm2.201
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发表时间：
2020-11
影响因子：
10.6
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Li H;Hu Y;Jin Y;Zhu Y;Hao Y;Liu F;Yang Y;Li G;Song X;Ye Y;Xiang S;Gao Y;Zhu J;Zhang Y;Jiang L;Huang W;Zhu J;Wu X;Liu Y
摘要背景长链非编码RNA（lncRNA）是哺乳动物转录组中的重要因子，介导了多种生物学和病理学过程。肝脏是胆囊癌（GBC）远处转移的最常见部位，并导致大多数GBC相关死亡。lncRNA如何影响GBC转移尚不完全清楚。结果发现一种新的lncRNA（lncRNA in GBC associated with liver metastasis，lncGALM）在肿瘤患者和有肝转移的移植瘤中高表达。GBC患者中lncGALM升高也与生存率降低相关。在体外和体内，lncGALM增强GBC细胞的侵袭和迁移。lncGALM通过竞争性结合并灭活miR-200家族成员发挥海绵的作用，miR-200家族成员增加上皮间质转化相关转录因子ZEB 1和ZEB 2，导致成纤维细胞表型和N-钙粘蛋白表达增加。此外，lncGALM与IL-1β mRNA结合并稳定介导肝窦内皮细胞（LSEC）凋亡的IL-1β基因。表达lncGALM的LiM 2-NOZ细胞获得了很强的迁移和粘附LSEC的能力，促进LSEC凋亡，从而促进肿瘤细胞外渗和扩散。结论lncGALM通过促进GBC细胞的迁移、侵袭、肝停滞和外渗，通过侵袭-转移级联反应促进GBC肝转移。靶向lncGALM可能对GBC患者中肝转移的发展具有保护作用。
Abstract Background Long noncoding RNAs (lncRNA) represent significant factors of the mammalian transcriptome that mediates varied biological and pathological processes. The liver is the most common site for gallbladder cancer (GBC) distant metastasis and contributes to the majority of GBC‐related death. How lncRNA affects GBC metastasis is not completely understood. Results A novel lncRNA termed lncGALM (lncRNA in GBC associated with liver metastasis) was discovered to be highly expressed in cancer patients and xenografted tumors with liver metastasis. Elevated lncGALM in GBC patients also correlated to decreased survival. Invasion and migration of GBC cells were enhanced through lncGALM, both in vitro and in vivo. lncGALM functioned as sponges by competitively binding to and inactivating miR‐200 family members, which increase epithelial‐mesenchymal transition‐associated transcription factor ZEB1 and ZEB2, leading to a fibroblastic phenotype and increased expression of N‐cadherin. In addition, lncGALM bound to IL‐1β mRNA and stabilized the IL‐1β gene that mediates liver sinusoidal endothelial cell (LSECs) apoptosis. lncGALM‐expressing LiM2‐NOZ cells acquired a strong ability to migrate and adhere to LSECs, promoting LSECs apoptosis and therefore facilitating tumor cell extravasation and dissemination. Conclusions lncGALM promotes GBC liver metastasis by facilitating GBC cell migration, invasion, liver arrest, and extravasation via the invasion‐metastasis cascade. Targeting lncGALM may be protective against the development of liver metastasis in GBC patients.
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影响因子：
12.3
作者：
Rigoutsos I;Lee SK;Nam SY;Anfossi S;Pasculli B;Pichler M;Jing Y;Rodriguez-Aguayo C;Telonis AG;Rossi S;Ivan C;Catela Ivkovic T;Fabris L;Clark PM;Ling H;Shimizu M;Redis RS;Shah MY;Zhang X;Okugawa Y;Jung EJ;Tsirigos A;Huang L;Ferdin J;Gafà R;Spizzo R;Nicoloso MS;Paranjape AN;Shariati M;Tiron A;Yeh JJ;Teruel-Montoya R;Xiao L;Melo SA;Menter D;Jiang ZQ;Flores ER;Negrini M;Goel A;Bar-Eli M;Mani SA;Liu CG;Lopez-Berestein G;Berindan-Neagoe I;Esteller M;Kopetz S;Lanza G;Calin GA
通讯作者：
Calin GA
影响因子：
24.5
作者：
Hur K;Toiyama Y;Takahashi M;Balaguer F;Nagasaka T;Koike J;Hemmi H;Koi M;Boland CR;Goel A
通讯作者：
Goel A
DOI：
10.15252/embj.201694912
发表时间：
2017-08-15
期刊：
The EMBO journal
影响因子：
--
作者：
Reid SE;Kay EJ;Neilson LJ;Henze AT;Serneels J;McGhee EJ;Dhayade S;Nixon C;Mackey JB;Santi A;Swaminathan K;Athineos D;Papalazarou V;Patella F;Román-Fernández Á;ElMaghloob Y;Hernandez-Fernaud JR;Adams RH;Ismail S;Bryant DM;Salmeron-Sanchez M;Machesky LM;Carlin LM;Blyth K;Mazzone M;Zanivan S
通讯作者：
Zanivan S
外泌体传输的 lncARSR 通过充当竞争性内源性 RNA 促进肾癌舒尼替尼耐药
影响因子：
50.3
作者：
Qu, Le;Ding, Jin;Wang, Lin-Hui
通讯作者：
Wang, Lin-Hui
CERNA假设：隐藏RNA语言的Rosetta石头？
影响因子：
64.5
作者：
Salmena L;Poliseno L;Tay Y;Kats L;Pandolfi PP
通讯作者：
Pandolfi PP