The majority of the human genome is not translated into proteins but can be transcribed into RNA. Even though the resulting non-coding RNAs (ncRNAs) do not encode for proteins, they contribute to diseases such as cancer. Here, we review examples of the functions of ncRNAs in liver cancer and their potential use for the detection and treatment of liver cancer.
The recognition of functional roles for transcribed long non-coding RNA (lncRNA) has provided a new dimension to our understanding of cellular physiology and disease pathogenesis. LncRNAs are a large group of structurally complex RNA genes that can interact with DNA, RNA or protein molecules to modulate gene expression and to exert cellular effects through diverse mechanisms. The emerging knowledge regarding their functional roles and their aberrant expression in disease states emphasizes the potential for lncRNA to serve as targets for therapeutic intervention. In this concise review, we outline the mechanisms of action of lncRNAs, their functional cellular roles, and their involvement in disease. Using liver cancer as an example, we provide an overview of the emerging opportunities and potential approaches to target lncRNA dependent mechanisms for therapeutic purposes.
Background and Aims
Stem cell-based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem-cell based therapies.
Methods
Therapeutic effects of bone-marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by D-Galactosamine/TNF-α.
Results
Systemically administered EV derived from MSC accumulated within the injured liver following systemic administration, reduced hepatic injury, and modulated cytokine expression. Moreover, survival was dramatically increased by EV derived from either murine or human MSC. Similar results were observed with the use of cryopreserved mMSC-EV after 3 months. Y-RNA-1 was identified as a highly enriched non-coding RNA within hMSC-EV compared to cells of origin. Moreover, siRNA mediated knockdown of Y-RNA-1 reduced the protective effects of MSC-EV on TNFα/Act D-mediated hepatocyte apoptosis in vitro.
Conclusions
These data support a critical role for MSC derived EV in mediating reparative responses following hepatic injury, and provide compelling evidence to support the therapeutic use of MSC derived EV in fulminant hepatic failure.
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