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MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets
Journal article   Open access   Peer reviewed

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets

Samuel Swearson, Aseel O Rataan, Steven Eliason, Brad A Amendt, Yousef Zakharia, Aliasger K Salem, Thai Ho and Youcef M Rustum
International journal of molecular sciences, Vol.23(10), p.5604
01/01/2022
DOI: 10.3390/ijms23105604
PMCID: PMC9147802
PMID: 35628416
url
https://doi.org/10.3390/ijms23105604View
Published (Version of record) Open Access

Abstract

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC.
 Angiogenesis Biomarkers Cell Differentiation Drug Resistance Genes Hypoxia Kidney Cancer RNA Tumors Biopsy Clear cell-type renal cell carcinoma Differentiation Drug dosages Epithelial cells Epithelium Hypoxia-inducible factors Kidneys Laboratories Matching miRNA p53 Protein Patients Ribonucleic acid Selenium Statistical analysis Therapeutic targets Tumor cell lines Tumor suppressor genes Vascular endothelial growth factor VHL protein

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