Title: The Role of MicroRNAs in Cancer Progression
Part 1: Introduction
MicroRNAs (miRNAs) are small non-coding RNA molecules that play crucial roles in various cellular processes, including regulation of gene expression. These molecules are approximately 22 nucleotides long and exert their regulatory functions by binding to the 3′ untranslated region (UTR) of target messenger RNA (mRNA), leading to mRNA degradation or inhibition of protein translation (1). It is estimated that miRNAs can regulate the expression of up to 60% of protein-coding genes, making them essential players in cellular homeostasis and disease development (2).
In recent years, there has been an increasing interest in understanding the involvement of miRNAs in cancer progression. Cancer is a complex and heterogeneous disease characterized by uncontrolled cell proliferation, invasion, and metastasis. The dysregulation of multiple genes is often responsible for driving these processes. Consequently, dysregulation of miRNA expression and function has been implicated in various aspects of cancer development and progression, making them potential targets for cancer therapy (3).
Part 2: Dysregulation of miRNAs in Cancer
2.1. Oncogenic miRNAs
Several miRNAs have been identified as oncogenic miRNAs, also known as oncomiRs. These miRNAs are upregulated in cancer cells and promote cancer progression through their effects on target gene expression. One well-characterized oncomiR is miR-21, which is frequently upregulated in various cancer types, including breast, lung, and colorectal cancer. miR-21 promotes tumorigenesis by targeting tumor suppressor genes involved in cell cycle regulation, apoptosis, and DNA repair (4).
Another well-studied oncomiR is miR-155, which is overexpressed in many hematopoietic malignancies, including leukemia and lymphoma. miR-155 promotes cancer progression by targeting multiple tumor suppressor genes involved in immune response regulation and apoptosis (5).
2.2. Tumor suppressor miRNAs
In contrast to oncomiRs, tumor suppressor miRNAs are downregulated in cancer cells. These miRNAs typically target oncogenes and other genes involved in promoting cell growth, invasion, or metastasis. Loss of tumor suppressor miRNA function can lead to increased expression of these cancer-promoting genes, contributing to tumor development and progression.
One prominent example of a tumor suppressor miRNA is miR-34a, which is frequently silenced in a variety of cancer types, including colorectal, breast, and pancreatic cancer. miR-34a exerts its tumor suppressor function by targeting multiple genes involved in cell cycle regulation, apoptosis, and DNA repair pathways (6).
Another well-known tumor suppressor miRNA is let-7. Downregulation of let-7 has been observed in several cancer types, including lung, breast, and ovarian cancer. Let-7 functions as a tumor suppressor by targeting multiple oncogenes involved in cell proliferation, differentiation, and epithelial-mesenchymal transition (7).
Part 3: Impact of miRNA Dysregulation on Cancer Hallmarks
3.1. Cell proliferation and apoptosis
Dysregulated miRNA expression can greatly impact cell proliferation and apoptosis, two critical processes in cancer progression. Oncogenic miRNAs can promote cell proliferation by targeting tumor suppressor genes involved in cell cycle regulation or cell growth inhibition. Additionally, oncomiRs can inhibit apoptosis by targeting pro-apoptotic genes or regulators of apoptosis pathways.
Conversely, tumor suppressor miRNAs can inhibit cell proliferation by targeting oncogenes involved in promoting cell growth or cell cycle progression. Tumor suppressor miRNAs can also promote apoptosis by directly targeting anti-apoptotic genes or by regulating key pro-apoptotic proteins.
3.2. Invasion and metastasis
The acquisition of invasive and metastatic capabilities is a hallmark of cancer progression. Dysregulation of miRNA expression can influence this process by regulating the expression of genes involved in cell adhesion, migration, and invasion.
Several miRNAs have been implicated in promoting cancer cell invasion and metastasis. For example, miR-10b is upregulated in breast cancer and has been shown to promote invasion and metastasis by targeting genes involved in cell adhesion and extracellular matrix remodeling (8).
On the other hand, certain miRNAs possess antimetastatic properties and inhibit cancer cell invasion and metastasis. One example is miR-335, which is frequently downregulated in breast and lung cancer. miR-335 inhibits metastasis by targeting multiple genes involved in cell motility and invasion, thereby suppressing the metastatic potential of cancer cells (9).
In conclusion, miRNAs play a significant role in the development and progression of cancer. Dysregulation of miRNA expression and function can contribute to the proliferation, invasion, and metastasis of cancer cells. Understanding the specific roles of different miRNAs in cancer progression can provide valuable insights into the underlying mechanisms and may lead to the development of novel therapeutic strategies. Further research is needed to uncover the full extent of miRNA involvement in cancer and to explore their potential as diagnostic biomarkers and therapeutic targets.
