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In the vast starry sky of life sciences, microRNAs (miRNAs) are leading the new direction of gene expression research with their unique regulatory roles. With the announcement of the 2024 Nobel Prize in Physiology or Medicine, research in this field has been pushed to a new climax. American scientists Victor Ambros and Gary Ruvkun were jointly honored for their discovery of miRNAs and their key role in post-transcriptional gene regulation.
miRNA Discovery
In 1993, Ambrose and Rufkun almost simultaneously discovered the LIN-4 gene in the cryptic nematode Cryptomeria showyi, which does not encode a protein but is transcribed to produce a 22-bp segment of microRNAs (miRNAs). This microRNA inhibits the expression of the LIN-14 gene, a nuclear protein, and thus regulates nematode development. They hypothesized that the mechanism of this repression lies in the ability of lin-4 to complement a unique repeat region in the 3'UTR region of the LIN-14 mRNA. This discovery did not attract much attention at the time, and it was widely believed that this was a specific regulatory mechanism present in Cryptomeria hirsuta.
It was not until 7 years later that Rufkun discovered a second miRNA, "let-7", which can also regulate nematode development by binding to the 3'UTR region of some target gene mRNAs, and demonstrated that it is highly conserved in the animal kingdom and can appear relatively stably across different between species. This suggests that miRNAs are a widespread regulatory mechanism. As more and more miRNAs are being discovered, with 1,917 human miRNAs included in miRBase by 2023, miRNAs can be involved in the regulation of many physiological mechanisms and can be used as markers for certain diseases, the role of miRNAs is becoming increasingly important.
What is miRNA?
miRNA, or microRNA, is a class of small RNA molecules usually around 20 to 25 nucleotides in length. They are generated by genome coding, and after a series of complex processing, they finally become regulatory molecules with specific functions. miRNA's sequence specificity enables it to bind to the 3' untranslated region (3'UTR) of the target mRNA through base complementary pairing, thus affecting the stability of the target mRNA or the translation process, and thus regulating the level of gene expression.
- Seeking MicroRNA (miRNA) Collaboration with BOC Sciences
BOC Sciences offers a comprehensive range of miRNA services, including miRNA synthesis, modification, identification and analysis. Our team uses advanced technology and expertise to provide customers with high-quality miRNA products that support their needs in basic research, drug development and clinical applications. Whether it is the synthesis of specific mirnas or the analysis of miRNA expression, we are committed to providing our customers with customized solutions to advance science. We look forward to working with our partners to advance the research and application of miRNAs, and to further promote greater scientific breakthroughs in miRNAs that have won the Nobel Prize in Biomedicine!
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miRNA Function
MicroRNAs do not encode proteins, but instead function by regulating the expression of other genes. They regulate gene expression primarily at the post-transcriptional level, which means that they affect mRNA stability and the translation process rather than mRNA synthesis. microRNAs usually bind to complementary sequences of the target mRNA molecule, which usually results in degradation of the mRNA or inhibition of its translation into a protein. This regulation can reduce the production of specific proteins and thus affect cell behavior and function. MicroRNAs are found in a wide variety of organisms, including plants, animals, and some viruses. they play important roles in different biological processes, such as development, cell differentiation, and disease genesis. microRNAs are involved in a number of biological processes, including cell proliferation, differentiation, apoptosis (programmed cell death), and immune responses. They have a wide range of effects on cellular phenotypes and physiological states of organisms by regulating networks of multiple genes.
Application of miRNA
miRNAs play crucial regulatory roles in organisms. They can participate in a variety of physiological processes such as cell differentiation, proliferation, apoptosis, etc., and have a profound impact on cell fate and function. By regulating gene expression networks, miRNAs are able to finely regulate the developmental and physiological processes of organisms, ensuring that organisms are able to adapt to environmental changes and maintain homeostasis. In addition, aberrant expression of miRNAs is closely related to the occurrence of a variety of diseases, such as cancer, neurological disorders, cardiovascular diseases, and so on. Therefore, miRNAs have not only become important markers for disease diagnosis, but also provide new strategies for disease treatment.
miRNA as a Biomarker for Disease Diagnosis
miRNAs show great potential in the diagnosis of many diseases, especially in the field of cancer. miRNA expression patterns change significantly in different types of cancers and are highly specific. Therefore, miRNAs can be used as important indicators for disease diagnosis and grading.
- Hepatocellular Carcinoma
Studies have shown that the expression levels of specific miRNAs (e.g., miR-767-5p and miR-1180-3p) are significantly elevated in tumor tissues of patients with hepatocellular carcinoma, displaying strong specificity.
- Lung Adenocarcinoma
Certain miRNAs (e.g., miR-148a-5p, miR-31-5p, miR-548v, and miR-550a-5p) can be used as a prognostic tool for patients with lung adenocarcinoma.
- Ovarian Cancer
Serum-derived small extracellular vesicle (sEV) miRNAs have shown good performance in the differentiation of benign and ovarian cancer malignancy.
- Pancreatic Cancer
The miRNA methylation level can be used as an important biomarker for the diagnosis of early pancreatic cancer, and its sensitivity and specificity are even better than some traditional tumor markers.
- Gastric Cancer
Blood miRNA can be used as a marker for early screening and early diagnosis of gastric cancer. In addition, miRNAs have shown potential in determining the benign or malignant nature of thyroid nodules, and related products such as ThyGenX and ThyraMIR have been included in the U.S. health insurance. Studies have also shown that miRNAs are associated with neurodegenerative diseases and cardiovascular diseases, although research in these areas is still in its early stages. As miRNAs continue to evolve in the field of disease diagnostics, several miRNA diagnostic kits have been approved by relevant regulatory agencies.
- GASTROClearTM: Developed by Mirxes Forerunner, GASTROClearTM uses blood miRNA as a marker for early screening of gastric cancer. It is approved in Singapore and the EU, and is in large-scale clinical trials in China. The kit requires only 5 milliliters of blood to screen people at high risk for gastric cancer, and has a high sensitivity of 87.5% for stage I gastric cancer.
- ThyGenX and ThyraMIR: These two products are used to determine the benign or malignant nature of thyroid nodules and have been included in the U.S. health insurance.
- Urine miRNA Prostate Cancer Detection Kit: launched by miR Sentinel, Inc. and recognized as a "Breakthrough Innovative Technology" by the U.S. FDA.
As a new generation of disease diagnostic markers, miRNAs show great potential in early screening, diagnosis and prognostic monitoring of cancer and many other diseases. In the future, miRNA therapeutics may become an important part of personalized medicine and precision medicine, helping to achieve early detection and treatment of diseases.
miRNA in Disease Treatment
The development of miRNA as a new strategy for disease treatment and the current development of small nucleic acid drugs is a research hotspot in the field of life science and medicine. Small nucleic acid drugs are drugs that can utilize small nucleic acid molecules such as siRNA , miRNA and antisense oligonucleotide (ASO) to specifically silence the expression of disease genes in order to cure specific diseases. Small nucleic acid drugs are mainly categorized into siRNA, miRNA, ASO, small activating RNA (saRNA ), aptamer , transporter RNA (tRNA ) fragments, and antibody-ribonucleic acid-coupled drugs (ARC). Compared with conventional drugs, small nucleic acid drugs have the advantages of being highly targeted, having fewer side effects, and being widely applicable. Their mechanism of action involves finely regulating or silencing the expression of disease-related genes, thereby blocking the disease progression process. This strategy of treating diseases at their root causes demonstrates great potential for diseases that are difficult to cure with conventional drugs, such as certain hereditary diseases, cancers and viral infections.
miRNA Detection Methods
There are various miRNA detection methods for different research and clinical application scenarios. The following are some commonly used miRNA detection methods:
Northern Blotting Method
This is a traditional detection method that can detect mature miRNAs and their precursors, but suffers from the disadvantages of low throughput, time-consuming, easy degradation, and low sensitivity.
Fluorescence Quantitative PCR
Real-time fluorescence quantitative PCR has become a routine and reliable technique for detecting miRNA expression due to its advantages of large dynamic range, high sensitivity, and high sequence specificity. This method converts the target miRNA into cDNA by reverse transcription, followed by PCR for real-time fluorescence detection .
Microarray Technology
This is a rapid, high-throughput method for the detection of miRNAs. The microarray technique uses labeled probes to generate sample RNAs by reverse transcription and detects these fluorescent motifs or biotin-labeled cDNAs using solid-phase oligonucleotides that have the same sequence as the target miRNA .
Digital PCR (Digital PCR, dPCR)
dPCR is an absolute quantitative method that enables detection at the single-molecule level by distributing the sample into thousands of microdroplets for PCR amplification .
Next Generation Sequencing
NGS is currently the most commonly used method for detecting targeted miRNAs and novel miRNAs, and is capable of processing millions of sequence reads in a short period of time while maintaining a high degree of sensitivity and specificity. Unlike other methods used for miRNA detection, NGS is not limited to known miRNAs, which makes it the method of choice for most studies today.
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