Park Jinjoo, Jeong Sunjoo
National Research Lab for RNA Cell Biology, Department of Molecular Biology, Dankook University, Yongin, Gyeonggi-do, Republic of Korea.
Oncotarget. 2015 Oct 27;6(33):34658-68. doi: 10.18632/oncotarget.5778.
RMRP, the RNA component of mitochondrial RNA processing endoribonuclease, is a non-coding RNA (ncRNA) part of the RNase MRP complex functioning in mitochondrial and ribosomal RNA processing. Even though various mutations in the RMRP gene are linked to developmental defects and pathogenesis, its relevance to cancer etiology has not been well established. Here we examined the expression of RMRP and found a significant increase in colorectal and breast cancer patient tissues. So we tested whether the oncogenic signaling pathways, Wnt/β-catenin and Hippo/YAP pathways, are relevant to the enhanced expression of RMRP in cancer cells because of the predicted β-catenin/TCF and YAP/TBX5 elements in the upstream regions of the RMRP gene. As expected, Wnt signal activation significantly induced the RMRP transcription thru β-catenin and YAP transcription factors. More importantly, YAP protein was critical for RMRP transcription by association to the proximal site near the transcription start site of the RMRP gene, a Pol III promoter, along with β-catenin and TBX5 proteins. We propose that the interplay of Wnt and Hippo signaling pathways could regulate target genes, coding or non-coding, by the β-catenin/YAP/TBX5 transcription complex in cancer cells.
线粒体RNA加工内切核糖核酸酶的RNA组分RMRP是核糖核酸酶MRP复合体的非编码RNA（ncRNA）部分，在线粒体和核糖体RNA加工中发挥作用。尽管RMRP基因的各种突变与发育缺陷和发病机制有关，但其与癌症病因的相关性尚未完全明确。在此，我们检测了RMRP的表达，发现其在结直肠癌和乳腺癌患者组织中显著增加。由于在RMRP基因上游区域预测存在β-连环蛋白/TCF和YAP/TBX5元件，我们测试了致癌信号通路Wnt/β-连环蛋白和Hippo/YAP通路是否与癌细胞中RMRP的表达增强有关。正如预期的那样，Wnt信号激活通过β-连环蛋白和YAP转录因子显著诱导了RMRP转录。更重要的是，YAP蛋白通过与RMRP基因转录起始位点附近的近端位点（一个Pol III启动子）结合，与β-连环蛋白和TBX5蛋白一起，对RMRP转录至关重要。我们提出，Wnt和Hippo信号通路的相互作用可能通过癌细胞中的β-连环蛋白/YAP/TBX5转录复合体调节靶基因（编码或非编码）。
