Document Details

Document Type : Article In Journal 
Document Title :
Cyclin D1 as a therapeutic target of renal cell carcinoma- a combined transcriptomics, tissue microarray and molecular docking study from the Kingdom of Saudi Arabia
Cyclin D1 as a therapeutic target of renal cell carcinoma- a combined transcriptomics, tissue microarray and molecular docking study from the Kingdom of Saudi Arabia
 
Document Language : English 
Abstract : Background: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. Methods: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC. Molecular pathway analysis was done to identify the canonical pathways and their role in RCC. Tissue microarrays (TMA) based immunohistochemical stains were used to validate the protein expression of cyclinD1 (CCND1) and were scored semi-quantitatively from 0 to 3+ on the basis of absence or presence of staining intensity in the tumor cell. Statistical analysis determined the association of CCND1 expression with RCC. Molecular docking analyses were performed to check the potential of two natural inhibitors, rutin and curcumin to bind CCND1. Results: We detected 1490 significantly expressed genes (1034, upregulated and 456, downregulated) in RCC using cutoff fold change 2 and p value < 0.05. Hes-related family bHLH transcription factor with YRPW motif 1 (HEY1), neuropilin 2 (NRP2), lymphoid enhancer-binding factor 1 (LEF1), and histone cluster 1 H3h (HIST1H3H) were most upregulated while aldolase B, fructose-bisphosphate (ALDOB), solute carrier family 12 (SLC12A1), calbindin 1 (CALB1) were the most down regulated genes in our dataset. Functional analysis revealed Wnt/β-catenin signaling as the significantly activated canonical pathway (z score = 2.53) involving cyclin D1 (CCND1). CCND1 was overexpressed in transcriptomic studies (FC = 2.26, p value = 0.0047) and TMA results also showed the positive expression of CCND1 in 53 % (73/139) of RCC cases. The ligands – rutin and curcumin bounded with CCND1 with good affinity. Conclusion: CCND1 was one of the important upregulated gene identified in microarray and validated by TMA. Docking study showed that CCND1 may act as a potential therapeutic target and its inhibition could focus on the migratory, invasive, and metastatic potential of RCC. Further in vivo and in vitro molecular studies are needed to investigate the therapeutic target potential of CCND1 for RCC treatment. 
ISSN : 1471-2407 
Journal Name : BMC cancer 
Volume : 16 
Issue Number : 2 
Publishing Year : 1437 AH
2016 AD 
Article Type : Article 
Added Date : Tuesday, July 18, 2017 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Sajjad KarimKarim, Sajjad ResearcherDoctorate 
Jaudah A Al-MaghrabiAl-Maghrabi, Jaudah AResearcherDoctorate 
Hasan M FarsiFarsi, Hasan MResearcherDoctorate 
Ahmad J Al-SayyadAl-Sayyad, Ahmad JResearcherDoctorate 
Hans-Juergen SchultenSchulten, Hans-Juergen ResearcherDoctorate 
Abdelbaset BuhmeidaBuhmeida, Abdelbaset ResearcherDoctorate 
Zeenat MirzaMirza, Zeenat ResearcherDoctorate 
Alaa A Al-boogmiAl-boogmi, Alaa AResearcher  
Fai T AshganAshgan, Fai TResearcher  
Manal M ShabaadShabaad, Manal MResearcherMaster 
Hend F NourEldinNourEldin, Hend FResearcherMaster 
Khalid M. Al-GhamdiAl-Ghamdi, Khalid M.ResearcherDoctorate 
Adel AbuzenadahAbuzenadah, Adel ResearcherDoctorate 
Adeel G ChaudharyChaudhary, Adeel GResearcherDoctorate 
Mohammed H Al-QahtaniAl-Qahtani, Mohammed HResearcherDoctorate 

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