The 2024 Nobel Prize in Physiology or Medicine has once again brought the spotlight onto the field of gene regulation. This year, American scientists Victor Ambros and Gary Ruvkun were honored with the prestigious award for their pioneering research on microRNA and its role in post-transcriptional gene regulation. Their groundbreaking discoveries not only opened new horizons in understanding gene regulation but also offered new perspectives and methods for studying and treating hematological diseases such as leukemia.

The Discovery and Fundamental Characteristics of microRNA

MicroRNAs (miRNAs) are a class of small RNA molecules, approximately 22 nucleotides long, that play key roles in gene regulation. They regulate gene expression by binding to the 3′ untranslated region (3’UTR) of target mRNAs, typically inducing repression or degradation of these mRNAs. The discovery of microRNA dates back to 1993, when Victor Ambros and Gary Ruvkun identified this novel small RNA, called lin-4 RNA, in Caenorhabditis elegans. Initially, this finding did not draw much attention, but subsequent research revealed the crucial role of microRNA in gene regulation.

Today, the human genome encodes over a thousand different microRNAs, which are involved in a wide range of normal and disease-related activities. Abnormal microRNA regulation has been closely linked to the onset and progression of numerous diseases, including leukemia, lung cancer, colorectal cancer, diabetes, and neurological disorders.

The Role of microRNA in Hematological Diseases

In recent years, an increasing number of studies have found that microRNA plays a significant role in hematological diseases such as leukemia. The occurrence and development of leukemia are often accompanied by abnormal expression of specific microRNAs. For instance, certain microRNAs may be overexpressed oncogenically in leukemia cells, while others may exhibit tumor-suppressive downregulation. These aberrantly expressed microRNAs affect various processes, such as tumor cell proliferation, apoptosis, and differentiation, by regulating related gene expression. Researchers have identified specific microRNAs closely associated with the development of leukemia, such as miR-374 and miR-198, which are altered in acute leukemia and potentially linked to tumor cell therapy.

MicroRNA as Diagnostic Biomarkers

MicroRNAs not only exist stably within cells but can also be secreted into bodily fluids, making them promising candidates for disease diagnosis. In hematological diseases like leukemia, specific microRNA expression levels undergo significant changes, serving as valuable diagnostic markers. For example, detecting microRNAs in a patient’s blood can help assess the malignancy of diffuse large B-cell lymphoma (DLBCL), aiding in risk stratification and treatment planning. Similarly, in acute leukemia, different microRNA expression profiles are closely correlated with distinct disease types and therapeutic responses. Therefore, microRNA analysis holds promise as a sensitive and specific biomarker for diagnosing leukemia, offering critical insights for clinical decision-making.

MicroRNA as a New Therapeutic Strategy

The regulatory properties of microRNAs present great potential for leukemia treatment. By targeting specific microRNAs, it is possible to modulate gene expression to achieve therapeutic effects. Researchers are actively exploring new methods to utilize microRNA characteristics for diagnostic and therapeutic interventions, aiming to manipulate their expression for leukemia treatment. For instance, inhibitors are being developed to target oncogenic microRNAs, suppressing tumor cell proliferation and increasing the sensitivity of chemotherapy drugs. Conversely, for tumor-suppressive microRNAs, promoting their expression can induce apoptosis and inhibit tumor growth.

Additionally, microRNAs can serve as markers for evaluating drug efficacy and safety. In cancer research, microRNA biomarkers are recognized as indicators of resistance to cancer treatment. By monitoring the expression levels of specific microRNAs, it is possible to predict a patient’s response and resistance to chemotherapy drugs, guiding clinical treatment and personalized therapeutic strategies.

MicroRNA Research in Hematopoietic Stem Cell Transplantation

Studies have shown that microRNA expression levels can be significant predictors of post-transplant complications and relapse risk in hematopoietic stem cell transplantation. By assessing specific microRNA levels in patients, it is possible to identify and address potential rejection reactions and relapse risks in time, improving the success rate of transplantation and overall patient survival.

Moreover, microRNAs are closely associated with the occurrence and development of certain hereditary blood disorders. Mutations in genes encoding microRNAs may lead to congenital hearing loss, eye and skeletal diseases, among other conditions. These findings not only highlight the critical role of microRNAs in hereditary blood disorders but also offer new avenues for diagnosing and treating related diseases.

Outlook and Challenges

As research into microRNAs continues to deepen, the future looks promising for their role in studying and applying treatments for leukemia and other hematological diseases. However, challenges remain, such as accurately detecting specific microRNA expression levels in patients, effectively intervening and regulating their expression, and evaluating the safety and efficacy of microRNA-based therapies. These questions require further in-depth exploration by researchers.

With ongoing advancements in high-throughput sequencing, bioinformatics, and gene-editing technologies, these challenges and issues are expected to be resolved, driving forward the research and application of microRNAs in leukemia and other hematological diseases, leading to greater breakthroughs and progress.