Exosomal lncRNA TUG1 from cancer-associated fibroblasts promotes liver cancer cell migration, invasion, and glycolysis by regulating the miR-524-5p/SIX1 axis

Cellular & Molecular Biology Letters

Jiantao Mo¹  Jingjing Huang¹  Le Lu¹  Qiaoxin Li¹  Meng Fan¹  Hongwei Lu¹  Xuanbo Da¹ 

[1] Department of General Surgery, The Second Affiliated Hospital of Xi’an Jiaotong University, No.157, West 5th Road, 710004, Xi’an, China;

关键词: Long noncoding RNA;    Taurine upregulated gene 1;    Hepatocellular carcinoma;    microRNA;    Sine oculis homeobox homolog 1;    Exosomes;   

DOI  :  10.1186/s11658-022-00309-9

来源: Springer

【 摘 要 】

BackgroundIncreasing evidence suggests that taurine upregulated gene 1 (TUG1) is crucial for tumor progression; however, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms are not well characterized.MethodsThe expression levels of TUG1, miR-524-5p, and sine oculis homeobox homolog 1 (SIX1) were determined using quantitative real-time PCR. The regulatory relationships were confirmed by dual-luciferase reporter assay. Cell proliferation and invasion were assessed using Cell Counting Kit 8 and transwell assays. Glucose uptake, cellular levels of lactate, lactate dehydrogenase (LDH), and adenosine triphosphate (ATP) were detected using commercially available kits. Silencing of TUG1 or SIX1 was performed by lentivirus transduction. Protein levels were measured by immunoblotting.ResultsCancer-associated fibroblasts (CAFs)-secreted exosomes promoted migration, invasion, and glycolysis in HepG2 cells by releasing TUG1. The promotive effects of CAFs-secreted exosomes were attenuated by silencing of TUG1. TUG1 and SIX1 are targets of miR-524-5p. SIX1 knockdown inhibited the promotive effects of miR-524-5p inhibitor. Silencing of TUG1 suppressed tumor growth and lung metastasis and therefore increased survival of xenograft model mice. We also found that TUG1 and SIX1 were increased in HCC patients with metastasis while miR-524-5p was decreased in HCC patients with metastasis.ConclusionsCAFs-derived exosomal TUG1 promoted migration, invasion, and glycolysis in HCC cells via the miR-524-5p/SIX1 axis. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for HCC in future.

【 授权许可】

CC BY