Identification and targeting of metastatic biomarkers for hepatocellular carcinoma therapeutics using small molecules library of curcumin analogues
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Published on: March 14, 2019
Ayushi Gupta1, Princy Choudhary1, Sangeeta Singh2
1Department of Applied Sciences, Indian Institute of Information Technology, Allahabad, Devghat, Jhalwa, Prayagraj, 211015, Uttar Pradesh, India.
Abstract:
The understanding of the molecular basis of complex diseases like hepatocellular carcinoma (HCC) needs large datasets of multiple genes and proteins involved in different phenomenon of its development. This study focuses on the molecular basis of HCC and the development of therapeutic strategies. We analyzed a dataset of 5475 genes (Homo sapiens) involved in HCC hallmarks, involving comprehensive data on multiple genes and frequently mutated genes. As HCC is characterized by metastasis, angiogenesis, and oxidative stress, exploration of genes associated with them has been targeted. Through gene ontology, functional characterization, and pathway enrichment analysis, we identified target proteins such as Lysyl oxidase, Survivin, Cofilin, and Cathepsin B. A library of curcumin analogs was used to target these proteins. Tetrahrydrocurcumin showed promising binding affinities for all four proteins, suggesting its potential as an inhibitor against these proteins for HCC therapy.
Insights
This study identifies key proteins involved in hepatocellular carcinoma (HCC) development and evaluates curcumin analogs as potential inhibitors. Tetrahydrocurcumin shows promise for targeting these proteins in HCC therapy.
Area of Science:
- Molecular Biology
- Oncology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) is a complex disease requiring deep understanding of its molecular underpinnings.
- Large datasets of genes and proteins are crucial for elucidating HCC development and therapeutic strategies.
Purpose of the Study:
- To investigate the molecular basis of hepatocellular carcinoma (HCC).
- To identify potential therapeutic targets and evaluate novel inhibitors for HCC treatment.
Main Methods:
- Analysis of a dataset comprising 5475 Homo sapiens genes associated with HCC hallmarks.
- Utilized gene ontology, functional characterization, and pathway enrichment analysis to identify target proteins.
- Screened a library of curcumin analogs for binding affinity against identified HCC-associated proteins.
Main Results:
- Identified four key target proteins: Lysyl oxidase, Survivin, Cofilin, and Cathepsin B, crucial in HCC metastasis, angiogenesis, and oxidative stress.
- Tetrahydrocurcumin demonstrated significant binding affinities to all four identified target proteins.
- Tetrahydrocurcumin emerged as a potential therapeutic agent for hepatocellular carcinoma.
Conclusions:
- Tetrahydrocurcumin exhibits potential as an inhibitor for Lysyl oxidase, Survivin, Cofilin, and Cathepsin B.
- This finding suggests a promising therapeutic strategy for hepatocellular carcinoma (HCC) using curcumin analogs.
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