Department of Urology, Xijing Hospital of Air Force Medical University, West Changle Road 127, Xi'an, China.
Department of Hepatobiliary Surgery, Xijing Hospital of Air Force Medical University, Xi'an, China.
J Transl Med. 2024 Mar 9;22(1):255. doi: 10.1186/s12967-024-05048-3.
Benign prostatic hyperplasia (BPH) is common in elder men. 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.
Four datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. Cell clusters and specific metabolism pathways were analyzed. 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.
A total of 17 DEGs were identified by merging three bulk RNA-seq datasets. The findings of integrated single-cell analysis showed that NRK remarkably upregulated in fibroblasts and SM cells of hyperplasia prostate. Meanwhile, NRK was upregulated in BPH samples and localized almost in stroma. The expression level of NRK was significantly correlated with IPSS and Q of BPH patients. 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. Meanwhile, induced fibrosis and EMT process were rescued by knockdown of NRK. 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.
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. NRK may play important roles in the development of BPH and may be a promising therapeutic target for BPH/LUTS.
良性前列腺增生（BPH）在老年男性中很常见。本研究旨在鉴定增生前列腺中的差异表达基因（DEGs），并探讨 Nik 相关激酶（NRK）在 BPH 中的作用。
获取了包括三个批量和一个单细胞 RNA-seq（scRNA-seq）在内的四个数据集，以进行综合生物信息学分析。分析了细胞簇和特定代谢途径。通过 RT-PCR、western-blot、免疫组织化学染色、流式细胞术、划痕愈合试验、Transwell 试验和 CCK-8 试验研究了 NRK 的定位、表达和功能活性。
通过合并三个批量 RNA-seq 数据集，共鉴定出 17 个 DEGs。综合单细胞分析的结果表明，NRK 在增生前列腺的成纤维细胞和 SM 细胞中显著上调。同时，NRK 在 BPH 样本中上调，几乎定位于基质中。NRK 的表达水平与 BPH 患者的 IPSS 和 Q 显著相关。NRK 沉默抑制了基质细胞的增殖、迁移、纤维化和 EMT 过程，促进了细胞凋亡和诱导细胞周期停滞，而在前列腺上皮细胞中过表达 NRK 则显示出相反的结果。同时，NRK 的敲低可挽救纤维化和 EMT 过程。此外，NRK 的表达水平与α-SMA、胶原-I 和 N-钙粘蛋白呈正相关，与 E-钙粘蛋白呈负相关。
我们的新数据表明，NRK 在增生前列腺中上调，并与前列腺基质细胞的增殖、凋亡、细胞周期、迁移、纤维化和 EMT 过程相关。NRK 可能在 BPH 的发展中起重要作用，可能是 BPH/LUTS 的有前途的治疗靶点。
