Wnt activated β-catenin and YAP proteins enhance the expression of non-coding RNA component of RNase MRP in colon cancer cells.

Jinjoo Park,Sunjoo Jeong

doi:10.18632/oncotarget.5778

Abstract

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.

Highlights

Recent advances of transcriptome analysis envision multiple functions for various non-coding RNAs, but their crucial roles in the survival, proliferation and growth of organisms remain elusive [1, 2]
Even though the RNA component of mitochondrial RNA processing endoribonuclease (RMRP) gene harbors the RNA polymerase III (Pol III) promoter [27], here we demonstrate that RMRP transcription is elevated in cancer cells by β-catenin and YAP activation
RMRP expression level is higher in malignant cells and cancer patient tissues Since the functions of RNase MRP should be related to the rapid proliferation of cancer cells, we first analyzed the RMRP expression level in patient tissues and cancer cells by RT-PCR as well as by real-time qRTPCR

Summary

Introduction

Recent advances of transcriptome analysis envision multiple functions for various non-coding RNAs (ncRNAs), but their crucial roles in the survival, proliferation and growth of organisms remain elusive [1, 2]. RMRP forms the RNase MRP complex required for pre-rRNA processing to 5.8S rRNA [5, 6] and for mitochondrial RNA processing [7]. In addition to these established functions, additional functions of RNase MRP have been recently proposed [8]. Despite such critical cellular functions of RNase MRP, how the expression level of RMRP is regulated by cellular components is not understood at the present time. Wnt signaling is critical for the development and homeostasis in metazoans with β-catenin being a critical transcription activator [9]. It is clear that Wnt signal activation is important in the tumorigenesis of various human cancers, some with complicated signaling networks [11]

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