Chenmeng Li1,2, Bei Pan1,2, Xuhong Wang1,2, Xiangxiang Liu1,2, Jian Qin1,2, Tianyi Gao2,3, Huiling Sun2,3, Yuqin Pan4,5, Shukui Wang6,7,8. 1. School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. 2. General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. 3. Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211100, Jiangsu, China. 4. General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. panyuqin01@163.com. 5. Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211100, Jiangsu, China. panyuqin01@163.com. 6. School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China. sk_wang@njmu.edu.cn. 7. General Clinical Research Center, Nanjing First Hospital of Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, Jiangsu, China. sk_wang@njmu.edu.cn. 8. Jiangsu Collaborative Innovation Center on Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 211100, Jiangsu, China. sk_wang@njmu.edu.cn.
Abstract
PURPOSE: Long intergenic non-coding RNA LINC01088 is a newly discovered long non-coding RNA (lncRNA). Its biological function in colorectal cancer (CRC) remains unknown. METHODS: Here, 36 paired CRC and para-cancerous tissues were collected. In vitro, fluorescence in situ hybridization (FISH) assay, qPCR, western blotting analysis and cellular functional experiments, RNA immunoprecipitation (RIP) assay and dual-luciferase reporter system analysis were performed. In vivo, xenograft tumor mouse models were generated. Besides, patient-derived intestinal organoid (PDO) was generated ex vivo. RESULTS: We found that LINC01088 was significantly upregulated in colorectal cancer tissues and CRC cell lines compared to adjacent normal tissues and colonic epithelial cells. High LINC01088 levels were correlated with adverse outcomes in patients with CRC. LINC01088 was mainly located in the cytoplasm. LINC01088 knockdown suppressed the proliferation, migration, invasion, and immune escape of colorectal cancer cells. Mechanistically, LINC01088 bound directly to miR-548b-5p and miR-548c-5p that were significantly upregulated Ras GTPase-activating protein-binding proteins 1 (G3BP1) and programmed death ligand 1 (PD-L1) expression, altering CRC cell phenotypes. In mouse xenograft models, LINC01088 knockdown restrained CRC tumor growth and lung metastasis. Furthermore, G3BP1 overexpression reversed LINC01088-knockdown-mediated inhibitory effects on tumor growth. Notably, LINC01088 knockdown downregulated PD-L1 expression, while G3BP1 overexpression restored PD-L1 expression in xenograft tumors. Besides, LINC01088 knockdown repressed CRC organoid growth ex vivo. CONCLUSION: Overall, these findings suggested that LINC01088 directly targeted miR-548b-5p and miR-548c-5p, promoting G3BP1 and PD-L1 expression, which facilitated colorectal cancer progression and immune escape.
PURPOSE: Long intergenic non-coding RNA LINC01088 is a newly discovered long non-coding RNA (lncRNA). Its biological function in colorectal cancer (CRC) remains unknown. METHODS: Here, 36 paired CRC and para-cancerous tissues were collected. In vitro, fluorescence in situ hybridization (FISH) assay, qPCR, western blotting analysis and cellular functional experiments, RNA immunoprecipitation (RIP) assay and dual-luciferase reporter system analysis were performed. In vivo, xenograft tumor mouse models were generated. Besides, patient-derived intestinal organoid (PDO) was generated ex vivo. RESULTS: We found that LINC01088 was significantly upregulated in colorectal cancer tissues and CRC cell lines compared to adjacent normal tissues and colonic epithelial cells. High LINC01088 levels were correlated with adverse outcomes in patients with CRC. LINC01088 was mainly located in the cytoplasm. LINC01088 knockdown suppressed the proliferation, migration, invasion, and immune escape of colorectal cancer cells. Mechanistically, LINC01088 bound directly to miR-548b-5p and miR-548c-5p that were significantly upregulated Ras GTPase-activating protein-binding proteins 1 (G3BP1) and programmed death ligand 1 (PD-L1) expression, altering CRC cell phenotypes. In mouse xenograft models, LINC01088 knockdown restrained CRC tumor growth and lung metastasis. Furthermore, G3BP1 overexpression reversed LINC01088-knockdown-mediated inhibitory effects on tumor growth. Notably, LINC01088 knockdown downregulated PD-L1 expression, while G3BP1 overexpression restored PD-L1 expression in xenograft tumors. Besides, LINC01088 knockdown repressed CRC organoid growth ex vivo. CONCLUSION: Overall, these findings suggested that LINC01088 directly targeted miR-548b-5p and miR-548c-5p, promoting G3BP1 and PD-L1 expression, which facilitated colorectal cancer progression and immune escape.
Authors: Aaron J Franke; William Paul Skelton; Jason S Starr; Hiral Parekh; James J Lee; Michael J Overman; Carmen Allegra; Thomas J George Journal: J Natl Cancer Inst Date: 2019-11-01 Impact factor: 13.506
Authors: G J Freeman; A J Long; Y Iwai; K Bourque; T Chernova; H Nishimura; L J Fitz; N Malenkovich; T Okazaki; M C Byrne; H F Horton; L Fouser; L Carter; V Ling; M R Bowman; B M Carreno; M Collins; C R Wood; T Honjo Journal: J Exp Med Date: 2000-10-02 Impact factor: 14.307
Authors: Bo Li; Eric Severson; Jean-Christophe Pignon; Haoquan Zhao; Taiwen Li; Jesse Novak; Peng Jiang; Hui Shen; Jon C Aster; Scott Rodig; Sabina Signoretti; Jun S Liu; X Shirley Liu Journal: Genome Biol Date: 2016-08-22 Impact factor: 13.583