Introduction:
The most significant vital organ in the human body is the liver which usually weighs around three pounds and is located on the upper right side of the abdomen. The liver plays a vital role in many functions, which regulate and metabolize many enzymes and drugs for the body, to work efficiently and healthily.
What Are the Main Functions of the Liver?
The main functions of the liver are:
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Production of essential protein in blood plasma.
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Natural detoxification of the body.
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Significant role in blood clotting.
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Converting food into energy.
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Production of bile. An essential role of bile is breaking down fats and flushing the toxins from the body.
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It helps in metabolizing a wide range of drugs.
A wide range of diseased conditions affects liver function in many ways.
Hepatocellular carcinoma is one of them; it occurs predominantly in severe cases of liver cirrhosis. An innovative RNA-based approach enhances endogenous albumin production while reducing liver tumor burden.
What Is Novel RNA Oligonucleotide?
Oligonucleotides are short DNA or RNA molecules with many forensics, research, and genetic testing applications. These nucleotide acids are vital for artificial gene synthesis, PCR (polymerase chain reaction), DNA (deoxyribonucleic acid) sequencing, molecular cloning, and molecular probes. Oligonucleotides are usually found as short RNA(Ribonucleic acid) molecules that regulate gene expression like microRNA. or in degradation derived from the breakdown of large nucleic acid molecules.
What Is RNA (Ribonucleic Acid) Activation?
It was first described in 2006, and it has been reported as short double-stranded RNAs targeted to promote the region of a gene that can activate its transcription. These small activating RNAs have been shown to activate various genes in several mammalian species. This technology provides a new research tool for selective gene activation and a novel therapeutic approach for diseases in which endogenous gene expression has been regulated through mutation or translational repression.
What Is Hepatocellular Carcinoma And Other Preferred Methods of Treatment?
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer.
It occurs most commonly in people with chronic liver diseases such as cirrhosis caused by hepatitis B and hepatitis C infection. There are many preferred methods for treatment of this condition which include:
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Surgery.
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Liver transplant surgery.
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Destroying liver cancer cells with extreme heat and extreme cold.
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Chemotherapy or radiation directed at cancer cells.
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Immunotherapy.
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Targeted drug therapy.
What Is Targeted Drug Therapy?
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Eukaryotic cells (clear cells that have a nuclear membrane surrounding the nucleus) use RNA complementarity to regulate gene expression. Classic RNA interference pathway uses double-stranded short interfering RNAs to get down gene expression through the RNA-induced silencing complex (RISC).
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RNA oligonucleotides can target genes and transfer transcriptional activation of genes referred to as RNA activation (RNAa), antigene RNAs, and short activating RNA (saRNA).
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Short activating RNA-induced genes appear in mammalian species; it works as a potential therapy for the treatment of hepatocellular carcinoma and prostate cancer, promising a novel approach for adjuvant treatment.
What Are the Materials and Methods of Short-Activating RNA Therapy?
Methods of designing short-activating RNA therapy:
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Animal experiments.
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Nuclease activity.
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Gene microarray profiling.
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Assessment of tumor burden.
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Immunostaining.
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Quantitative reverse transcription.
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Polymerase chain reaction (qRT-PCR).
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Gene ontology enrichment analysis.
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Gene methylation analysis.
What Is the Detailed View of Materials and Methods of RNA Oligonucleotide?
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Design of Short-Acting RNA Oligonucleotide (Short DNAs or RNAs): The gene sequence of albumin and C/EBP alpha was selected to design short-acting RNA molecules.
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Transfection of SA RNA Oligonucleotides Into HEPG2 and Rat Liver Epithelial Cell Lines: HepG2 is a liver cell derived from human hepatoblastoma and is free of known hepatotropic viral agents that are involved in specific metabolic functions.
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Albumin Enzyme-Linked Immunosorbent Assay (ELISA): Rat liver cells and HepG2 cells are cultured in phenol-red free RPMI (Roswell park memorial institute medium) in the presence of charcoal-stripped fetal calf serum.
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WST-1 Assay: Cell proliferation is quantified following C/EBP alpha - Sa RNA transfection by mitochondrial dehydrogenase expression using WST-1 reagent.
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Isolation of Total RNA From Cell Lines: Total RNA extraction from cell lines was performed using an RNA aqueous-micro kit. Cells are centrifuged, followed by three pulses of sonication.
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Animal Experiments: Clinically relevant rat liver tumor in vivo therapy was reconstituted with 100ul of RNase or DNAse-free water.
How Is The Activation of RNA Helpful in HCC (Hepatocellular Carcinoma) Treatment?
In cases of hepatocellular carcinoma, inhibition of several genes has shown potential antitumor effects. Most of them provide proof of showing growth inhibition or induction of apoptosis (type of cell death) using hepatocellular carcinoma-derived cell lines in cell culture. Models have shown retardation growth in tumors, especially when cancer cells are transfected ex vivo.
Can Novel RNA Oligonucleotide Improve Liver Function?
Yes, novel RNA oligonucleotide improves liver function to a greater extent and is a successful mode of treatment in cases of HCC (hepatocellular carcinoma).
Conclusion:
In hepatocellular carcinoma patients who have a background of liver cirrhosis (end-stage liver disease) and account for 90% of all liver cancers, much progress has been made in targeting gene therapy. Therapies for liver tumors, both primary and secondary, and metastatic (spread of cancer cells) remain a challenge that needs new approaches. Transfer of genes to the majority of cancer cells is still unrealistic for solid tumors.
Hepatocellular carcinoma can be used to deliver gene therapy vectors inside tumors, increasing safety and efficacy. Gene therapy, especially novel RNA, will improve the management of liver cancer patients as a part of individualized multimodal therapy. Most of these therapeutic methods, like surgery, radiotherapy, chemotherapy, and biologics, are associated with variable decreases in liver dysfunction. Gene therapy with novel RNA oligonucleotide is a new approach to target liver cancer cells.
