Clear cell renal cell carcinoma (ccRCC) is one of the common subtypes of kidney cancer. Circular RNAs (circRNAs) act as competing endogenous RNAs (ceRNAs) to affect the expression of microRNAs (miRNAs), and hence the expression of genes involved in the development and progression of ccRCC. However, these interactions have not been sufficiently explored.
The differential expression of circRNAs (DEC) was extracted from the GEO database, and the expression of circRNAs was analyzed by the Limma R package. The interaction of miRNAs with circRNAs was predicted using (cancer-specific circRNA database) CSCD and circinteractome database. The genes affected by the miRNAs were predicted by miRwalk version 3, and the differential expression was retrieved using TCGA. Functional enrichment was assessed and a PPI network was created using DAVID and Cytoscape, respectively. The genes with significant interactions (hub-genes) were screened, and the total survival rate of ccRCC patients was extracted from the Gene Expression Profiling Interactive Analysis (GEPIA) database. To confirm the expression of OS genes we used the Immunohistochemistry (IHC) data and TCGA database. The correlation between gene expression and immune cell infiltration was investigated using TIMER2.0. Finally, potential drug candidates were predicted by the cMAP database.
Four DECs (hsa_circ_0003340, hsa_circ_0007836, hsa_circ_0020303, and hsa_circ_0001873) were identified, along with 11 interacting miRNAs (miR-1224-3p, miR-1294, miR-1205, miR-1231, miR-615-5p, miR-940, miR-1283, and miR-1305). These miRNAs were predicted to affect 1282 target genes, and function enrichment was used to identify the genes involved in cancer biology. 18 hub-genes (CCR1, VCAM1, NCF2, LAPTM5, NCKAP1L, CTSS, BTK, LILRB2, CD53, MPEG1, C3AR1, GPR183, C1QA, C1QC, P2RY8, LY86, CYBB, and IKZF1) were identified from a PPI network. VCAM1, NCF2, CTSS, LILRB2, MPEG1, C3AR1, P2RY8, and CYBB could affect the survival of ccRCC patients. The hub-gene expression was correlated with tumor immune cell infiltration and patient prognosis. Two potantial drug candidates, naphazoline and lithocholic acid could play a role in ccRCC therapy, as well other cancers.
This bioinformatics analysis brings a new insight into the role of circRNA/miRNA/mRNA interactions in ccRCC pathogenesis, prognosis, and possible drug treatment or immunotherapy.
Computers in biology and medicine. 2021 Nov 20 [Epub ahead of print]
Ghanbar Mahmoodi Chalbatani, Seyed Ali Momeni, Mohammad Hosein Mohammadi Hadloo, Zhina Karimi, Morteza Hadizadeh, Seyed Amir Jalali, Seyed Rouhollah Miri, Fereidoon Memari, Michael R Hamblin
Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran; Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran., Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, IR, Iran., Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran., Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran., Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ., Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ., Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA, 02114, USA. Electronic address: .