| Title | Long Noncoding RNA VESTAR Regulates Lymphangiogenesis and Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma by Enhancing VEGFC mRNA Stability |
| Authors | Wang, Yali Zhang, Weimin Liu, Wenzhong Huang, Lijie Wang, Yan Li, Dan Wang, Guangchao Zhao, Zitong Chi, Xinming Xue, Yu Song, Yongmei Liu, Xuefeng Zhan, Qimin |
| Affiliation | Chinese Acad Med Sci & Peking Union Med Coll, State Key Lab Mol Oncol, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ Beijing, Lab Mol Oncol,Canc Hosp & Inst, Beijing 100142, Peoples R China Dalian Med Univ, Inst Canc Stem Cell, Dalian 116044, Peoples R China Dalian Med Univ, Liaoning Key Lab Prote, Dalian, Peoples R China Peking Univ, Shenzhen Peking Univ, Hong Kong Univ Sci & Technol PKU HKUST, Med Ctr,Shenzhen Hosp, Shenzhen, Peoples R China Shenzhen Bay Lab, Inst Canc Res, Shenzhen, Peoples R China Chinese Acad Med Sci, Res Unit Mol Canc Res, Beijing, Peoples R China |
| Keywords | ENDOTHELIAL GROWTH-FACTOR NUCLEAR EXPORT FACTOR-C PROMOTES LYMPHANGIOGENESIS BLADDER-CANCER EXPRESSION NUMBER NXF1 PROLIFERATION MIGRATION |
| Issue Date | 15-Jun-2021 |
| Publisher | CANCER RESEARCH |
| Abstract | Lymph node metastasis is one of the most malignant clinical features in patients with esophageal squamous cell carcinoma (ESCC). Understanding the mechanism of lymph node metastasis will provide treatment strategies for patients with ESCC. Long noncoding RNAs (lncRNA) play a critical role in the development and progression of human cancers. However, the role and mechanism of lncRNAs in lymph node metastasis remain largely unknown. Here we show that VEGFC mRNA stability-associated long noncoding RNA (VESTAR) is involved in lymph node metastasis of ESCC. VESTAR was overexpressed in ESCC tissues and was predictive of poor prognosis in patients with ESCC. In ESCC, NXF1 and SRSF3 facilitated nuclear export of VESTAR to the cytoplasm, which was associated with lymph node metastasis. Depletion of VESTAR inhibited ESCC-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, VESTAR directly bound and stabilized VEGFC mRNA. VESTAR also interacted with HuR, a positive regulator of VEGFC mRNA stability, and increased HuR binding to VEGFC mRNA. Our study reveals a novel lncRNA-guided mechanism of lymph node metastasis in ESCC and may provide a potential target for treatment of ESCC lymphatic metastasis. Significance: These findings illustrate the lncRNA-guided regulation of VEGFC mRNA stability via direct RNA-RNA interactions, highlighting a therapeutic target for patients with ESCC with lymphatic metastasis. |
| URI | http://hdl.handle.net/20.500.11897/617889 |
| ISSN | 0008-5472 |
| DOI | 10.1158/0008-5472.CAN-20-1713 |
| Indexed | SCI(E) |
| Appears in Collections: | 北京肿瘤医院 深圳医院 |
