How can alteration in microRNA lead to overexpression?

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in regulating gene expression at the post-transcriptional level. They bind to complementary sequences in messenger RNA (mRNA) molecules, leading to mRNA degradation or translational repression. In recent years, researchers have discovered that alterations in microRNA expression can lead to overexpression of target genes, which may contribute to various diseases, including cancer. This article aims to explore the mechanisms by which alterations in microRNA can lead to overexpression and its implications in disease development.

1. MicroRNA dysregulation and gene expression

MicroRNAs are typically expressed at low levels, but their dysregulation can have profound effects on gene expression. There are several ways in which alterations in microRNA can lead to overexpression of target genes:

a. Loss of microRNA expression: When microRNA levels are reduced, the binding to target mRNA molecules is impaired, resulting in increased mRNA stability and translation. This can lead to overexpression of the target gene.

b. Gain of function mutations: Certain mutations in microRNA molecules can result in an increased binding affinity to target mRNA, leading to enhanced mRNA degradation or translational repression. This can also cause overexpression of the target gene.

c. Altered microRNA processing: The biogenesis of microRNAs involves a complex process that includes transcription, processing, and maturation. Any disruption in this process can lead to the production of abnormal microRNAs, which may have altered functions and contribute to overexpression of target genes.

2. Implications in disease development

Alterations in microRNA expression and function have been associated with various diseases, including cancer, cardiovascular diseases, and neurological disorders. Here are some examples of how alterations in microRNA can lead to overexpression and contribute to disease development:

a. Cancer: Aberrant microRNA expression is a hallmark of cancer. For instance, downregulation of tumor suppressor microRNAs can lead to overexpression of oncogenes, promoting cancer development and progression. Conversely, upregulation of oncomiRs can also contribute to overexpression of target genes, enhancing tumor growth and metastasis.

b. Cardiovascular diseases: MicroRNA dysregulation has been observed in cardiovascular diseases, such as myocardial infarction and atherosclerosis. For example, downregulation of microRNA-126 can lead to overexpression of VEGF-A, a pro-angiogenic factor, contributing to the development of atherosclerosis.

c. Neurological disorders: MicroRNA alterations have been implicated in neurological disorders, such as Alzheimer’s disease and Parkinson’s disease. For instance, downregulation of microRNA-9 can lead to overexpression of BACE1, a key enzyme in the amyloidogenic pathway, contributing to the development of Alzheimer’s disease.

3. Therapeutic implications

Understanding the mechanisms by which alterations in microRNA can lead to overexpression of target genes is crucial for the development of novel therapeutic strategies. Here are some potential therapeutic approaches:

a. MicroRNA mimics and inhibitors: Delivery of microRNA mimics can restore the normal expression of tumor suppressor microRNAs, while microRNA inhibitors can target oncogenic microRNAs, leading to downregulation of target genes.

b. RNA interference: RNA interference (RNAi) technology can be used to specifically target and silence overexpressed genes by using short interfering RNAs (siRNAs) or antisense oligonucleotides.

c. Gene editing: Techniques such as CRISPR/Cas9 can be employed to edit the genes responsible for microRNA dysregulation, restoring normal microRNA expression and function.

In conclusion, alterations in microRNA can lead to overexpression of target genes through various mechanisms, contributing to disease development. Understanding these mechanisms is essential for the development of novel therapeutic strategies targeting microRNA dysregulation. Further research is needed to elucidate the complex interplay between microRNAs and gene expression, leading to better treatment options for various diseases.