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Ferroptosis rewired: ncRNA gatekeepers as pharmacological targets in hepatocellular carcinoma
Abdulrahman T Ahmed1,2, Mahmood Jawad3, Gaurav Sanghvi4
1College of Nursing, University of Al Maarif, Ramadi, Al Anbar, 31001, Iraq. Abdulrahman.dheyab@uoa.edu.iq.
Abstract:
Hepatocellular carcinoma (HCC) can alter cellular programs, such as iron homeostasis and antioxidant defenses, creating a pathway to ferroptosis, an iron-dependent mechanism of cellular death, as a viable therapeutic approach. Non-coding RNAs (ncRNAs), including both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have recently been shown to be potent regulatory molecules involved in gene expression and cell fates, including apoptosis and inflammation. This review summarizes the current literature regarding ncRNAs' multiple and complex roles in mediating HCC ferroptosis. We focus on mechanistic insights into how ncRNAs regulate some major ferroptosis regulators (e.g., SLC7A11/GPX4 axis, iron metabolism, and lipid peroxidation). We also highlight recent research evidence of the interconnection between ncRNA-modulated regulation of ferroptosis and inflammation in HCC development. This review thoughtfully evaluates studies that have identified ncRNAs functioning as either promoters or suppressors of ferroptosis and their impacts on the inflammatory response within the tumor microenvironment. Finally, we discuss the prognostic roles of these ncRNAs and the potential for ncRNAs to be used as diagnostic and therapeutic biomarkers in HCC. Finally, through an accumulated body of literature, we try to create a cohesive understanding of ncRNAs' role in ferroptosis and inflammation in HCC, pointing to promising avenues for future research and clinical applications.
Insights
Non-coding RNAs (ncRNAs) significantly influence hepatocellular carcinoma (HCC) ferroptosis and inflammation. Understanding these ncRNA roles offers new diagnostic and therapeutic strategies for HCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) involves altered cellular processes like iron homeostasis and antioxidant defenses, leading to ferroptosis, a form of cell death.
- Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are key regulators of gene expression, influencing cell fates such as apoptosis and inflammation.
Purpose of the Study:
- To review the multifaceted roles of ncRNAs in mediating ferroptosis in HCC.
- To explore the mechanistic insights of ncRNA regulation on ferroptosis key players and lipid peroxidation.
- To highlight the interplay between ncRNA-regulated ferroptosis and inflammation in HCC development.
Main Methods:
- Comprehensive literature review of studies on ncRNAs, ferroptosis, and inflammation in HCC.
- Analysis of mechanisms by which ncRNAs regulate ferroptosis regulators (e.g., SLC7A11/GPX4 axis, iron metabolism).
- Evaluation of ncRNAs as promoters or suppressors of ferroptosis and their impact on the tumor microenvironment.
Main Results:
- ncRNAs intricately regulate major ferroptosis pathways, including the SLC7A11/GPX4 axis, iron metabolism, and lipid peroxidation in HCC.
- A significant interconnection exists between ncRNA-mediated ferroptosis regulation and the inflammatory response within the HCC tumor microenvironment.
- ncRNAs have been identified as both promoters and suppressors of ferroptosis, influencing HCC progression and inflammation.
Conclusions:
- ncRNAs play complex roles in regulating ferroptosis and inflammation in HCC, impacting disease development and progression.
- ncRNAs show potential as prognostic, diagnostic, and therapeutic biomarkers for HCC.
- Further research into ncRNA functions in HCC ferroptosis and inflammation may unveil novel clinical applications.
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