» Articles » PMID: 26859141

Integrated MicroRNA and MRNA Signature Associated with the Transition from the Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma Exemplified by MiR-146-5p

Overview
Journal PLoS One
Date 2016 Feb 10
PMID 26859141
Citations 66
Authors
Affiliations
Soon will be listed here.
Abstract

Background: MicroRNAs (miRNAs) regulate gene expression by interfering translation or stability of target transcripts. This interplay between miRNA and their mRNA has been proposed as an important process in cancer development and progression. We have investigated molecular networks impacted by predicted mRNA targets of differentially expressed miRNAs in patients with clear cell renal cell carcinoma (ccRCC) diagnosed with or without metastasis.

Material And Methods: miRNA and mRNA microarray expression profiles derived from primary ccRCC from patients with (16 samples) or without diagnosed metastasis (22 samples) were used to identify anti-correlated miRNA-mRNA interaction in ccRCC. For this purpose, Ingenuity pathway analysis microRNA Target Filter, which enables prioritization of experimentally validated and predicted mRNA targets was used. By applying an expression pairing tool, the analysis was focused on targets exhibiting altered expression in our analysis, finding miRNAs and their target genes with opposite or same expression. The resulting identified interactions were revalidated by RT-qPCR in another cohort of ccRCC patients. A selection of the predicted miRNA-mRNA interactions was tested by functional analyses using miRNA knockdown and overexpression experiments in renal cancer cell lines.

Results: Among the significantly differentially expressed miRNAs, we have identified three miRNAs (miR-146a-5p, miR-128a-3p, and miR-17-5p) that were upregulated in primary tumors from patients without metastasis and downregulated in primary tumors from patients with metastasis. We have further identified mRNA targets, which expression were inversely correlated to these 3 miRNAs, and have been previously experimentally demonstrated in cancer setting in humans. Specifically, we showed that CXCL8/IL8, UHRF1, MCM10, and CDKN3 were downregulated and targeted by miR-146a-5p. The interaction between miR-146a-5p and their targets CXCL8 and UHRF1 was validated in cell culture experiments.

Conclusions: We identified novel target genes of dysregulated miRNAs, which are involved in the transition from primary RCC without metastases into tumors generating distant metastasis.

Citing Articles

The systematic analysis of genes related to butyrate metabolism suggests that CDKN3 could serve as a promising therapeutic target for lung adenocarcinoma treatment.

Luan Y, Liang C, Han Q, Zhou X, Yang N, Zhao L BMC Cancer. 2025; 25(1):69.

PMID: 39806313 PMC: 11726977. DOI: 10.1186/s12885-024-13409-w.


Effectiveness and Mechanism of Resibufogenin on Human Renal Cancer Cell Caki-1.

Wu Y, Yang Y, Huang R, Li T, Wan C, Zhang L Biology (Basel). 2025; 13(12.

PMID: 39765731 PMC: 11673963. DOI: 10.3390/biology13121064.


Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma.

Ajadee A, Mahmud S, Hossain M, Ahmmed R, Ali M, Reza M PLoS One. 2024; 19(9):e0310843.

PMID: 39348357 PMC: 11441673. DOI: 10.1371/journal.pone.0310843.


Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.

Ahmed S, Sasikumar J, Laha S, Das S Cancer Metastasis Rev. 2024; 43(4):1353-1371.

PMID: 39240414 DOI: 10.1007/s10555-024-10209-3.


Oncogenic Roles of UHRF1 in Cancer.

Kim A, Benavente C Epigenomes. 2024; 8(3).

PMID: 39051184 PMC: 11270427. DOI: 10.3390/epigenomes8030026.


References
1.
Ma J, Peng J, Mo R, Ma S, Wang J, Zang L . Ubiquitin E3 ligase UHRF1 regulates p53 ubiquitination and p53-dependent cell apoptosis in clear cell Renal Cell Carcinoma. Biochem Biophys Res Commun. 2015; 464(1):147-53. DOI: 10.1016/j.bbrc.2015.06.104. View

2.
Butz H, Szabo P, Nofech-Mozes R, Rotondo F, Kovacs K, Mirham L . Integrative bioinformatics analysis reveals new prognostic biomarkers of clear cell renal cell carcinoma. Clin Chem. 2014; 60(10):1314-26. DOI: 10.1373/clinchem.2014.225854. View

3.
Gales D, Clark C, Manne U, Samuel T . The Chemokine CXCL8 in Carcinogenesis and Drug Response. ISRN Oncol. 2013; 2013:859154. PMC: 3810054. DOI: 10.1155/2013/859154. View

4.
Bronner C, Krifa M, Mousli M . Increasing role of UHRF1 in the reading and inheritance of the epigenetic code as well as in tumorogenesis. Biochem Pharmacol. 2013; 86(12):1643-9. DOI: 10.1016/j.bcp.2013.10.002. View

5.
Li M, Wang Y, Song Y, Bu R, Yin B, Fei X . MicroRNAs in renal cell carcinoma: a systematic review of clinical implications (Review). Oncol Rep. 2015; 33(4):1571-8. PMC: 4358077. DOI: 10.3892/or.2015.3799. View