A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma

Abstract

BackgroundClear cell renal cell carcinoma (ccRCC) is a urinary disease with high incidence. The high incidence of metastasis is the leading cause of death in patients with ccRCC. This study was aimed to identify the gene signatures during the metastasis of ccRCC.MethodsTwo datasets, including one gene expression profile dataset and one microRNA (miRNA) expression profile dataset, were downloaded from Gene Expression Omnibus (GEO) database. The integrated bioinformatics analysis was performed using the (limma) R package, miRWalk, DAVID, STRING, Kaplan-Meier plotter databases. Quantitative real-time polymerase chain reaction (qPCR) was conducted to validate the expression of differentially expressed genes (DEGs) and DE-miRNAs.ResultsIn total, 84 DEGs (68 up-regulated and 16 down-regulated) and 41 DE-miRNAs (24 up-regulated and 17 down-regulated) were screened from GSE22541 and GSE37989 datasets, respectively. Furthermore, 11 hub genes and 3 key miRNAs were identified from the PPI network, including FBLN1, THBS2, SCGB1A1, NKX2-1, COL11A1, DCN, LUM, COL1A1, COL6A3, SFTPC, SFTPB, miR-328, miR-502, and miR-504. The qPCR data showed that most of the selected genes and miRNAs were consistent with that in our integrated analysis. A novel mRNA-miRNA network, SFTPB-miR-328-miR-502-miR-504-NKX2-1 was found in metastatic ccRCC after the combination of data from expression, survival analysis, and experiment validation.ConclusionIn conclusion, key candidate genes and miRNAs were identified and a novel mRNA-miRNA network was constructed in ccRCC metastasis using integrated bioinformatics analysis and qPCR validation, which might be utilized as diagnostic biomarkers and molecular targets of metastatic ccRCC.

Evaluation of a blood miRNA/mRNA signature to follow-up Lu-PRRT therapy for G1/G2 intestinal neuroendocrine tumors

“…Moreover, each biomarker of our panel was described as dysregulated in both the tumor and peripheral blood compartments for patients with GI-NET, suggesting their specificity ( 33 ). We reveal on this preliminary study that combining mRNA and miRNA expression profiling could be an interesting option to use in order to assess patient sensitivity and outcome to LuPRRT as previously revealed for the diagnosis and prognosis of several cancers ( 34 – 36 ). Our miRNA/mRNA signature focusing on a combination of four mRNAs and three miRNAs should be able to detect the LuPRRT responders earlier than NETest.…”

RAI2 acts as a tumor suppressor with functional significance in gastric cancer

“…Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for obtaining the featured genes by PCA algorithm with “clusterProfiler”, “ggplot2” “enrichplot”, “org.Hs.eg.db”, using R package [ 15 ]. Terms were regarded as significantly enriched only with both P < 0.05 and q < 0.05.…”

“…STRING website ( https://cn.string-db.org/ ) was employed to build the PPI network of DEGs [ 15 ]. Cytoscape version 3.6.1 was then used for reconstruction, and nodes were selected to build a PPI network with a confidence level greater than 0.95.…”

LncRNA AGAP2 antisense RNA 1 stabilized by insulin-like growth factor 2 mRNA binding protein 3 promotes macrophage M2 polarization in clear cell renal cell carcinoma through regulation of the microRNA-9-5p/THBS2/PI3K-Akt pathway

“…Thrombospondin 2 (THBS2), a member of the calcium-binding glycoprotein family of stromal cells, is crucially involved in cell proliferation, adhesion and apoptosis. Many studies have found that THBS2 is highly expressed in different cancers, including RCC [38][39][40]. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway plays an important role not only in tumor progression but also in tumor response to cancer treatment [41][42][43].…”