MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma.

Lisa Kinget,Bram Boeckx,Cristina Rodríguez-Antona,Benoit Beuselinck,Maarten Albersen,Loïc Vanginderhuysen,Diether Lambrechts,Gabrielle Couchy,Marcella Baldewijns,Osvaldo Graña-Castro,Jessica Zucman-Rossi,Annelies Verbiest,Stefano Caruso,Lucía Inglada-Pérez,Eduard Roussel,Annouschka Laenen

doi:10.3390/cancers13071554

Abstract

Simple SummaryBone metastases cause substantial morbidity and implicate worse clinical outcomes for clear-cell renal cell carcinoma patients. MicroRNAs are small RNA molecules that modulate gene translation and are involved in the development of cancer and metastasis. We identified six microRNAs that are potentially specifically involved in metastasis to bone, of which two seem protective and four implicate a higher risk. This aids further understanding of the process of metastasizing to bone. Furthermore, these microRNA hold potential for biomarkers or therapeutic targets.Bone metastasis in clear-cell renal cell carcinoma (ccRCC) leads to substantial morbidity through skeletal related adverse events and implicates worse clinical outcomes. MicroRNAs (miRNA) are small non-protein coding RNA molecules with important regulatory functions in cancer development and metastasis. In this retrospective analysis we present dysregulated miRNA in ccRCC, which are associated with bone metastasis. In particular, miR-23a-3p, miR-27a-3p, miR-20a-5p, and miR-335-3p specifically correlated with the earlier appearance of bone metastasis, compared to metastasis in other organs. In contrast, miR-30b-3p and miR-139-3p were correlated with less occurrence of bone metastasis. These miRNAs are potential biomarkers and attractive targets for miRNA inhibitors or mimics, which could lead to novel therapeutic possibilities for bone targeted treatment in metastatic ccRCC.

Highlights

Bone metastases (BM) occur in about 22% to 35% of all metastatic clear-cell renal cell carcinoma patients [1,2]
Patients with synchronous BM or metastasis in all organs other than BM (MOTB) were excluded for analysis of TTBM or TTMOTB, respectively, resulting in patient groups of 106 and 72, respectively
We report correlations between the intratumoral expression of miRNAs and mRNA of genes involved in invasion and metastasis and in the development of BM

Summary

Introduction

Bone metastases (BM) occur in about 22% to 35% of all metastatic clear-cell renal cell carcinoma (ccRCC) patients [1,2]. They can give rise to skeletal related events (SREs) such as pain, hypercalcemia, pathologic fractures, and myelum compression, causing substantial morbidity. Preventing the occurrence of BM in ccRCC patients would provide substantial clinical benefit. Bone resorption inhibitors such as bisphosphonates or denosumab can reduce the number of SRE, though their impact on outcome is not precisely defined [6,7,8]. We demonstrated that higher receptor activator of nuclear factor κB (RANK) and lower osteoprotegerin (OPG) expression in the primary kidney tumor are correlated with the occurrence of BM [9], findings that were similar to those of Mikami et al [10]

Objectives

Methods

Results

Conclusion