Abstract
Non-small cell type lung cancer (NSCLC) is the most common malignancy and the leading cause of cancer related mortality. In this study, serine/threonine kinase 39 (STK39) was identified as an up-regulated gene in NSCLC tissues by next-generation RNA sequencing. Although STK39 gene polymorphisms may be prognostic of overall survival in patients with early stage NSCLC, the roles of STK39 in NSCLC cancer are poorly understood. In the current study, Genome Set Enrichment Analysis (GSEA) on the RNA-seq data of NSCLC specimens indicated that cancer-related process and pathways, including metastasis, cell cycle, apoptosis and p38 pathway, were significantly correlated with STK39 expression. STK39 expression was significantly increased in NSCLC cases and its protein expression was positively correlated with the poor tumor stage, large tumor size, advanced lymphnode metastasis and poor prognosis. Down-regulation of STK39 in NSCLC cells significantly decreased cell proliferation by blocking of cell cycle and inducing apoptosis. We also found that STK39 knockdown in NSCLC cells remarkably repressed cell migration and invasion. On the contrary, overexpression of STK39 in NSCLC cells had inverse effects on cell behaviors. Taken together, STK39 acts as a tumor oncogene in NSCLC and can be a potential biomarker of carcinogenesis.
Highlights
Lung cancer is the most common malignancy and the leading cause of cancer related mortality both in China and worldwide [1, 2]
Genome Set Enrichment Analysis (GSEA) on the RNA-seq data of Non-small cell type lung cancer (NSCLC) tissues indicated that cancer-related process and pathways (Supplementary Table S3 and Figure 1C), such as metastasis, cell cycle, apoptosis and p38 pathway, were significantly enriched in serine/threonine kinase 39 (STK39) higher expression tissues
We conducted RNA sequencing for 10 pairs of NSCLC and non-cancerous lung tissues, and identified a novel differential expressed genes (DEGs), STK39
Summary
Lung cancer is the most common malignancy and the leading cause of cancer related mortality both in China and worldwide [1, 2]. In the last few decades, with the advances in our knowledge of the molecular biology of tumors, targeted therapy has become an important strategy for treating lung cancer. Identifying novel diagnostic and prognostic markers using a more comprehensive approach would facilitate the development of new strategies for new therapeutic targets for NSCLC treatment. We applied RNA-Seq to sequence the whole transcriptomes of 10 pairs of NSCLC and adjacent noncancerous specimens. We identified serine/threonine kinase 39 (STK39), a member of the Ste20-like kinase family [7], as an up-regulated gene in NSCLC tissues as compared with non-cancerous tissues. Genome Set Enrichment Analysis (GSEA) on the RNA-seq data of NSCLC specimens indicated that STK39 expression was significantly correlated with cancer-related process and pathways, which suggest the involvement of STK39 in the progression of NSCLC. Further in vitro cell functional experiments and in vivo animal experiments suggested that STK39 might serve as an oncogene by increasing cell proliferation, migration and invasion
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