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Updated: Jul 11, 2025
Perturbations of Circulating miRNAs in Irritable Bowel Syndrome Detected Using a Multiplexed High-throughput Gene Expression Platform
Published on: November 30, 2016
Next generation sequencing uncovers multiple miRNAs associated molecular targets in gallbladder cancer patients
Rahul Saxena1, Baskar Chakrapani1, M P Sarath Krishnan1
1Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India.
Abstract:
Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.
Insights
This study identified 439 dysregulated microRNAs (miRNAs) in gallbladder cancer (GBC), revealing potential therapeutic targets. These findings support miRNA-based precision medicine for improved GBC treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gallbladder cancer (GBC) has limited treatment options beyond surgery, with current adjuvant therapies showing minimal efficacy.
- Advances in next-generation sequencing have highlighted the role of microRNAs (miRNAs) in cancer gene regulation.
- Understanding molecular pathways is crucial for developing targeted therapies in GBC.
Purpose of the Study:
- To identify microRNAs (miRNAs) that are dysregulated in gallbladder cancer (GBC).
- To explore the potential of these dysregulated miRNAs as therapeutic targets for GBC.
- To investigate novel, targeted treatment strategies for GBC using miRNA-based interventions.
Main Methods:
- Sequencing of miRNA expression in GBC and control tissue samples using the Illumina HiSeq platform.
- Utilizing Panther and Gene Ontology databases to analyze biological processes and related pathways.
- Identification and analysis of significantly differentially expressed miRNAs.
Main Results:
- Identified 439 significantly differentially expressed miRNAs in GBC, with 19 upregulated and 29 downregulated.
- Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum overload response, and negative regulation of androgen receptor (AR) signaling.
- Highly enriched pathways involved the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK, p53, and FAS signaling pathways. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified as potential therapeutic targets.
Conclusions:
- Dysregulated miRNAs in GBC present potential targets for novel therapeutic strategies.
- A combined approach using miRNA-based interventions could significantly improve treatment outcomes in GBC.
- This research underscores the importance of precision medicine, utilizing sense and anti-sense miRNAs for targeted GBC therapy.
