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lncRNA SYTL5-OT4 promotes vessel co-option by inhibiting the autophagic degradation of ASCT2.
Wen, Qing; Huang, Maohua; Xie, Jingwen; Liu, Runyu; Miao, Qun; Huang, Jinjun; Zhang, Junqiu; Lyu, Wenyu; Qi, Ming; Wu, Chunyi; Qi, Qi; Zhang, Zhijing; Deng, Rong; Wang, Chenran; Chen, Zhe-Sheng; Zhang, Dongmei; Ye, Wencai; Chen, Minfeng.
Afiliação
  • Wen Q; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Huang M; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Xie J; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Liu R; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Miao Q; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Huang J; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Zhang J; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Lyu W; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Qi M; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Wu C; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Qi Q; School of Medicine, Jinan University, Guangzhou 510632, China.
  • Zhang Z; School of Medicine, Jinan University, Guangzhou 510632, China.
  • Deng R; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
  • Wang C; College of Pharmacy, Jinan University, Guangzhou 510632, China.
  • Chen ZS; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Institute for Biotechnology, St. John's University, NY 11439, USA. Electronic address: chenz@stjohns.edu.
  • Zhang D; College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China. Electronic address: dmzhang701@jnu.edu.cn.
  • Ye W; College of Pharmacy, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China. Electronic address: chywc@aliyun.com.
  • Chen M; College of Pharmacy, Jinan University, Guangzhou 510632, China. Electronic address: minfengchen@jnu.edu.cn.
Drug Resist Updat ; 69: 100975, 2023 Jul.
Article em En | MEDLINE | ID: mdl-37207473
AIMS: Vessel co-option is responsible for tumor resistance to antiangiogenic therapies (AATs) in patients with colorectal cancer liver metastasis (CRCLM). However, the mechanisms underlying vessel co-option remain largely unknown. Herein, we investigated the roles of a novel lncRNA SYTL5-OT4 and Alanine-Serine-Cysteine Transporter 2 (ASCT2) in vessel co-option-mediated AAT resistance. METHODS: SYTL5-OT4 was identified by RNA-sequencing and verified by RT-qPCR and RNA fluorescence in situ hybridization assays. The effects of SYTL5-OT4 and ASCT2 on tumor cells were investigated by gain- and loss-of-function experiments, and those of SYTL5-OT4 on ASCT2 expression were analyzed by RNA immunoprecipitation and co-immunoprecipitation assays. The roles of SYTL5-OT4 and ASCT2 in vessel co-option were detected by histological, immunohistochemical, and immunofluorescence analyses. RESULTS: The expression of SYTL5-OT4 and ASCT2 was higher in patients with AAT-resistant CRCLM. SYTL5-OT4 enhanced the expression of ASCT2 by inhibiting its autophagic degradation. SYTL5-OT4 and ASCT2 promoted vessel co-option by increasing the proliferation and epithelial-mesenchymal transition of tumor cells. Combination therapy of ASCT2 inhibitor and antiangiogenic agents overcame vessel co-option-mediated AAT resistance in CRCLM. CONCLUSION: This study highlights the crucial roles of lncRNA and glutamine metabolism in vessel co-option and provides a potential therapeutic strategy for patients with AAT-resistant CRCLM.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Longo não Codificante / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Drug Resist Updat Assunto da revista: ANTINEOPLASICOS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Longo não Codificante / Neoplasias Hepáticas Limite: Humans Idioma: En Revista: Drug Resist Updat Assunto da revista: ANTINEOPLASICOS Ano de publicação: 2023 Tipo de documento: Article País de afiliação: China