In other organs or tissues, NRK also exhibit different functions including modulating cell proliferation, apoptosis, migration, cell cycle, inflammation regulation and cytoskeletal organization. Most studies of NRK focused on its crucial role of regulating placenta development. NRK, a gene on the X-chromosome and a member of the germinal center kinase (GCK) family subgroup IV, was firstly cloned from mice and found in skeletal muscle during mouse embryogenesis in 1996. Our current analysis combined RNA-seq and scRNA-seq datasets to explore the possible biomarkers of BPH and demonstrated that the Nik related kinase (NRK) might be a new therapeutic target for BPH/LUTS. However, integrative analysis using multiple datasets are few. A recent study also investigated therapeutic targets in BPH using single-cell RNA-seq (scRNA-seq) data. Functional activity and related pathways of biomarkers including BMP5, NELL2, IGF1, CXCL13, MXRA5 and GPX3 were identified from many analyses using gene microarrays and RNA-seq datasets. With the development of bioinformatics analysis in recent years, many studies have given new insight into pathophysiology mechanism of BPH. Therefore, fibrosis and EMT might be a promising therapeutic target for BPH/LUTS. EMT is characterized as increasing mesenchymal-like cells derived from the prostatic epithelium and TGF-β is thought to play a key role in EMT. Meanwhile, epithelial-mesenchymal transition (EMT) also contributes to prostatic fibrosis and hyperplasia, which leads to BPH/LUTS progress. Fibrosis was proposed to be a new pathological mechanism of BPH and involved in the progress of LUTS, however, the current first-line oral medications (α1-blockers and 5-ARIs) have shown no effect on reverse or alleviation of fibrosis. Stroma myofibroblasts play pivotal role in the process of fibrosis that accumulation of which results in remodeling of the extracellular matrix (ECM) and tissue hardening by secreting large amounts of collagen proteins deposited. However, from the pathological aspect, besides the continuous nonmalignant proliferation of prostate cells, BPH tissues also exhibit stromal fibrosis. With regard to the pathogenesis of BPH/LUTS, some hypothesis have been proposed including growth factor, stromal-epithelial interaction, ratio between estrogen and androgen, chronic inflammation, genetic and familial factors, metabolic syndrome, autoimmunity and embryonic reawakening theory. To date, aging and testosterone are two defined independently risk factor of BPH/LUTS. Further and in-depth of investigations for therapeutic targets are of great significances. The dilemma in medical therapy of BPH/LUTS was probably due to its not-fully revealed etiology and pathogenesis. Despite current medical therapy such as α1-adrenoceptor antagonists (α1-blockers) and 5α-reductase inhibitors (5-ARIs) serve satisfactory, a portion of patients might experience complications or require further surgical interventions. NRK may play important roles in the development of BPH and may be a promising therapeutic target for BPH/LUTS.īenign prostatic hyperplasia (BPH) and its related lower urinary tract symptoms (LUTS) are very common in elder men, which affecting their quality of life. Our novel data identified NRK was upregulated in hyperplastic prostate and associated with prostatic stromal cell proliferation, apoptosis, cell cycle, migration, fibrosis and EMT process. Furthermore, expression level of NRK was positively correlated with that of α-SMA, collagen-I and N-cadherin, negatively correlated with that of E-cadherin. Meanwhile, induced fibrosis and EMT process were rescued by knockdown of NRK. Silencing of NRK inhibited stromal cell proliferation, migration, fibrosis and EMT process, promoted apoptosis and induced cell cycle arrest, while overexpression of NRK in prostate epithelial cells showed opposite results. The expression level of NRK was significantly correlated with IPSS and Q max of BPH patients. Meanwhile, NRK was upregulated in BPH samples and localized almost in stroma. The findings of integrated single-cell analysis showed that NRK remarkably upregulated in fibroblasts and SM cells of hyperplasia prostate. ResultsĪ total of 17 DEGs were identified by merging three bulk RNA-seq datasets. The localization, expression and functional activity of NRK was investigated via RT-PCR, western-blot, immunohistochemical staining, flow cytometry, wound healing assay, transwell assay and CCK-8 assay. Cell clusters and specific metabolism pathways were analyzed. Methodsįour datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. The current study aims to identify differentially expressed genes (DEGs) in hyperplastic prostate and to explore the role of Nik related kinase (NRK) in BPH. Benign prostatic hyperplasia (BPH) is common in elder men.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |