Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai 600020, Tamil Nadu, India.
Department of Molecular Oncology, Cancer Institute (WIA), Adyar, Chennai 600020, Tamil Nadu, India.
Gene. 2021 Jul 20;790:145697. doi: 10.1016/j.gene.2021.145697. Epub 2021 May 5.
Human Mitoribosomal Small Subunit unit (MRPS) family of genes appears to have role in cancer. Gene expression analysis of select MRPS genes (n = 9) in 15 cancer cell lines showed altered expression in cancer cells. Protein levels of MRPS6, MRPS23 showed significant overexpression in breast cancer cells and tissues. Interestingly, their overexpression did not correlate with mitochondrial ribosome translated COX2 protein levels in breast cancer. Subcellular fractionation analysis showed a distinct presence of MRPS23 in the nuclear fraction. GST/MRP6 and GST/MRPS23 pulldown assays identified 32 novel protein-protein interactions (PPIs) and MRPS23-RIPK3 interaction was validated. Co-expression module identification tool (CEMi) analysis of breast cancer gene expression and MRPS6 and MRPS23 interactions revealed hub interactions in gene expression modules having functional roles in cancer-associated cellular processes. Based on PPI network analysis a novel interaction MRPS23-p53 was validated. Knockdown of MRPS6 and MRPS23 decreased proliferation, expression of select mesenchymal markers, oncogenes, and increased expression of tumor suppressor genes. Taken together present study has revealed that MRPS6 and MRPS23 genes have pro-tumorigenic functions in breast cancer.
人类线粒体核糖体小亚基（MRPS）基因家族似乎在癌症中起作用。对 15 种癌细胞系中选定的 MRPS 基因（n=9）的基因表达分析显示，癌细胞中存在表达改变。MRPS6、MRPS23 的蛋白水平在乳腺癌细胞和组织中均显著过表达。有趣的是，它们的过表达与乳腺癌中线粒体核糖体翻译的 COX2 蛋白水平无关。亚细胞分级分析显示 MRPS23 明显存在于核部分。GST/MRP6 和 GST/MRPS23 下拉测定鉴定了 32 种新的蛋白质-蛋白质相互作用（PPIs），并验证了 MRPS23-RIPK3 相互作用。乳腺癌基因表达和 MRPS6 和 MRPS23 相互作用的共表达模块识别工具（CEMi）分析显示，在与癌症相关的细胞过程中具有功能作用的基因表达模块中存在着核心相互作用。基于蛋白质-蛋白质相互作用网络分析，验证了一种新的相互作用 MRPS23-p53。MRPS6 和 MRPS23 的敲低降低了增殖、选择的间充质标记物、癌基因的表达，并增加了肿瘤抑制基因的表达。综上所述，本研究揭示了 MRPS6 和 MRPS23 基因在乳腺癌中具有促进肿瘤发生的功能。
