LSH interacts with and stabilizes GINS4 transcript that promotes tumourigenesis in non-small cell lung cancer

Journal of Experimental & Clinical Cancer Research

  ^{1    2    2    2    2    2    2    2    2    2    2    2    2    3    4    5    5    6} 

[1] 0000 0001 0379 7164, grid.216417.7, Department of Oncology, Institute of Medical Sciences, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China;0000 0001 0379 7164, grid.216417.7, Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China;0000 0001 0379 7164, grid.216417.7, NHC Key Laboratory of Carcinogenesis of Ministry of Health (Central South University), Cancer Research Institute; School of Basic Medicine, Central South University, 410078, Changsha, Hunan, China;0000 0001 0379 7164, grid.216417.7, Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, 410078, Changsha, Hunan, China;0000 0001 0379 7164, grid.216417.7, NHC Key Laboratory of Carcinogenesis of Ministry of Health (Central South University), Cancer Research Institute; School of Basic Medicine, Central South University, 410078, Changsha, Hunan, China;0000 0001 0379 7164, grid.216417.7, Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, China;0000 0001 0379 7164, grid.216417.7, Department of Pathology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China;0000 0001 0379 7164, grid.216417.7, Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, China;0000000419368710, grid.47100.32, Department of Pathology, Yale School of Medicine, 06520, New Haven, CT, USA;

关键词: GINS4;    LSH;    mRNA stability;    Lung cancer;   

DOI  :  10.1186/s13046-019-1276-y

来源: publisher

【 摘 要 】

BackgroundElucidating mechanisms in oncogenes and epigenetic modifiers are needed to gain insights into the etiology and treatment of cancer, regulation of oncogene by chromatin modifiers at post-transcriptional level is critical and remains unclear. We have investigated the role of GINS4 in NSCLC.MethodsThe expression of chromatin modifier lymphoid-specific helicase (LSH) and GINS4 was assessed in tumor and normal tissue from 79 patients with NSCLC with clinical characteristics. HBE, A549, H358, and H522, PC9, 95C and 95D were cultured after overexpression or silencing of GIAT4RA. Cell proliferation assay, cell migration and invasion assays, plate colony formation assay, immunofluorescence assay, Operetta® high-content screening and analysis, Western blot analysis and Co-Immunoprecipitation (Co-IP) assay, RNA immunoprecipitation assay and tumor growth assay was used to address the potential interplay of between GINS4 and LSH, and the functional of GINS4.ResultsGINS4 is highly expressed in lung cancer cells and tissues, and GINS4 expression is not association with clinical risk factors, but linked with clinical stage and lymphatic metastasis status. Higher expression of GINS4 poorly linked with overall survival in lung adenocarcinomas. Furthermore, GINS4 promoted many characteristics of tumorigenesis including cell growth, clonal formation, migration and invasion, epithelial–mesenchymal transition, tumor sphere and tumor growth in vivo. Interestingly, our results demonstrated that LSH increases GINS4 expression through binding to 3’UTR region of GINS4 and stabilizing its mRNA levels. Finally, LSH overexpression rescues GINS4 knockdown-induced features.ConclusionsGINS4 facilitates lung cancer progression by promoting key characteristics of tumor potential, and LSH epigenetically interacts with and stabilizes GINS4 transcripts.

【 授权许可】

CC BY