Department of Convergence Medical Science and Biochemistry, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, Korea.
Int J Mol Sci. 2021 Mar 17;22(6):3052. doi: 10.3390/ijms22063052.
Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF-κκB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of gene in human cancers is not well understood. In this study, we suggested a possible transcription mechanism for the regulation of RKIP in human cancer cells. We found that Metadherin (MTDH) significantly repressed the transcriptional activity of gene. An analysis of publicly available datasets showed that the knockdown of in breast and endometrial cancer cell lines induced the expression RKIP. In addition, the results obtained from qRT-PCR and ChIP analyses showed that MTDH considerably inhibited RKIP expression. In addition, the RKIP transcript levels in -knockdown or -overexpressing MCF-7 cells were likely correlated to the protein levels, suggesting that MTDH regulates RKIP expression. In conclusion, we suggest that MTDH is a novel factor that controls the RKIP transcription, which is essential for cancer progression.
Raf 激酶抑制蛋白（RKIP），也称为磷脂酰乙醇胺结合蛋白 1（PEBP1），作为肿瘤抑制因子发挥作用，调节包括 ERK 和 NF-κκB 在内的几种信号通路。RKIP 在人类恶性肿瘤中严重下调，表明其与癌症转移和预后不良具有功能相关性。人类癌症中基因的转录调控机制尚不清楚。在这项研究中，我们提出了一种可能的转录机制，用于调节人类癌细胞中的 RKIP。我们发现 Metadherin（MTDH）显著抑制基因的转录活性。对公开可用数据集的分析表明，在乳腺癌和子宫内膜癌细胞系中敲低可诱导 RKIP 的表达。此外，qRT-PCR 和 ChIP 分析的结果表明，MTDH 可显著抑制 RKIP 的表达。此外，在 -knockdown 或 -overexpressing MCF-7 细胞中 RKIP 转录本水平可能与蛋白水平相关，表明 MTDH 调节 RKIP 表达。总之，我们认为 MTDH 是控制 RKIP 转录的新型因子，这对于癌症进展至关重要。
