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Cyclin D1 as a therapeutic target of renal cell carcinoma- a combined transcriptomics, tissue microarray and

Sajjad Karim1, Jaudah A Al-Maghrabi2,3, Hasan M A Farsi4

  • 1Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. skarim1@kau.edu.sa.

BMC Cancer
|October 22, 2016
PubMed
Abstract

Insights

This study identifies cyclin D1 (CCND1) as a key biomarker in metastatic renal cell carcinoma (RCC). Inhibiting CCND1 shows promise for treating advanced RCC, offering new therapeutic avenues.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Renal cell carcinoma (RCC) is a leading cause of cancer death with poor prognosis, especially at the metastatic stage.
  • Current systemic treatments are ineffective for metastatic RCC, highlighting the need for novel biomarkers and therapeutic targets.
  • Identifying effective inhibitors is crucial for managing advanced RCC.

Purpose of the Study:

  • To evaluate potential biomarkers for targeted therapy in metastatic RCC.
  • To identify effective inhibitors for treating the metastatic stage of RCC.
  • To explore the role of cyclin D1 (CCND1) as a therapeutic target.

Main Methods:

  • Transcriptomic profiling to identify differentially expressed genes in RCC.
  • Molecular pathway analysis to determine key signaling pathways involved in RCC.
  • Immunohistochemical validation of CCND1 protein expression using tissue microarrays (TMA).
  • Molecular docking to assess the binding potential of natural inhibitors (rutin, curcumin) to CCND1.

Main Results:

  • 1490 differentially expressed genes were identified in RCC, including upregulated genes like HEY1, NRP2, LEF1, HIST1H3H and downregulated genes like ALDOB, SLC12A1, CALB1.
  • Wnt/β-catenin signaling was identified as a significantly activated canonical pathway involving CCND1.
  • CCND1 was overexpressed in RCC (FC=2.26, p=0.0047) and detected in 53% of cases via TMA.
  • Rutin and curcumin demonstrated favorable binding affinity to CCND1.

Conclusions:

  • CCND1 is a significant upregulated gene in RCC, validated by TMA.
  • CCND1 represents a potential therapeutic target for inhibiting migration, invasion, and metastasis in RCC.
  • Further in vitro and in vivo studies are warranted to confirm CCND1's therapeutic potential in RCC treatment.
Keywords:
Cyclin D1Gene expression profilingMolecular dockingRenal cell carcinomaSaudi ArabiaTherapeutic targetTissue microarray

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