Background
Elucidating 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.
Methods
The 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.
Results
GINS4 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.
Conclusions
GINS4 facilitates lung cancer progression by promoting key characteristics of tumor potential, and LSH epigenetically interacts with and stabilizes GINS4 transcripts.
Electronic supplementary material
The online version of this article (10.1186/s13046-019-1276-y) contains supplementary material, which is available to authorized users.
Nasopharyngeal carcinoma (NPC) is one of the most prevailing cancers in southern China and southern Asia. Because of the nonspecific symptoms and lack of effective biomarker, most patients are diagnosed at advanced stages, resulting in poor 5-year survival rate. To identify a novel NPC biomarker facilitating early detection and effective therapy of NPC, a two-step strategy consisting of cancer cell-Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) procedure and aptamer-based purification approach was developed. Using cell-SELEX procedure, four aptamers (S3, S5, S12 and S27) differentiating the molecular differences between NPC cells and NP cells were successfully screened. Then, using aptamer-based protein purification, membrane protein CD109 was identified as the target of aptamer S3. CD109 protein was further identified to be over-expressed in NPC cell lines and clinic tissues, but not or low in NP cell line and clinic NP tissues, detected by western blot and immunohistochemistry experiments. Our study demonstrated that CD109 identified by cell-SELEX and aptamer-based purification strategy might be used as a potential NPC biomarker for early diagnosis and targeted therapy.
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