MicroRNAs in cell proliferation, cell death, and tumorigenesis

MicroRNAs in cell proliferation, cell death, and tumorigenesis

2006 | H-W Hwang and JT Mendell
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by targeting messenger RNAs (mRNAs). They play crucial roles in cell proliferation, differentiation, and apoptosis. Abnormal miRNA expression is a common feature of human malignancies, and miRNAs can act as oncogenes or tumor suppressors. This review discusses how miRNAs influence tumorigenesis by regulating these processes. MiRNAs are initially transcribed by RNA polymerase II as long primary transcripts (pri-miRNAs), which are processed in the nucleus by Drosha and DGCR8 to produce precursor miRNAs (pre-miRNAs). These are then exported to the cytoplasm and further processed by Dicer to generate mature miRNAs. The mature miRNA is incorporated into the RNA-induced silencing complex (RISC), where it guides the complex to target mRNAs, leading to either cleavage or translational repression. Early studies in C. elegans and Drosophila showed that miRNAs regulate developmental timing and cell fate. For example, lin-4 and let-7 miRNAs control developmental events. In cancer, miRNAs have been shown to regulate cell proliferation, apoptosis, and tumorigenesis. For instance, the mir-17 cluster is overexpressed in B-cell lymphomas and promotes oncogenesis. Conversely, let-7 miRNAs act as tumor suppressors by inhibiting oncogenes like RAS. Abnormal miRNA expression is associated with various cancers, including B-cell chronic lymphocytic leukemia (B-CLL), lung cancer, and breast cancer. miRNAs are often located in genomic regions that are frequently amplified, deleted, or rearranged in cancer. Studies have shown that miRNA profiles can distinguish between different cancer subtypes and predict prognosis. MiRNAs with proproliferative and antiapoptotic activity, such as miR-21, promote oncogenesis, while those with antiproliferative and proapoptotic activity, like let-7, act as tumor suppressors. The mir-17 cluster and miR-21 are examples of miRNAs that contribute to cancer progression. Additionally, miRNAs are involved in stem cell maintenance and cell cycle progression, highlighting their importance in both normal and pathological conditions. Understanding miRNA function in cancer is crucial for developing diagnostic and therapeutic strategies. However, identifying the critical targets of miRNAs and their tissue-specific functions remains a challenge. Continued research into miRNA biology will provide insights into cancer mechanisms and potential therapeutic targets.MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by targeting messenger RNAs (mRNAs). They play crucial roles in cell proliferation, differentiation, and apoptosis. Abnormal miRNA expression is a common feature of human malignancies, and miRNAs can act as oncogenes or tumor suppressors. This review discusses how miRNAs influence tumorigenesis by regulating these processes. MiRNAs are initially transcribed by RNA polymerase II as long primary transcripts (pri-miRNAs), which are processed in the nucleus by Drosha and DGCR8 to produce precursor miRNAs (pre-miRNAs). These are then exported to the cytoplasm and further processed by Dicer to generate mature miRNAs. The mature miRNA is incorporated into the RNA-induced silencing complex (RISC), where it guides the complex to target mRNAs, leading to either cleavage or translational repression. Early studies in C. elegans and Drosophila showed that miRNAs regulate developmental timing and cell fate. For example, lin-4 and let-7 miRNAs control developmental events. In cancer, miRNAs have been shown to regulate cell proliferation, apoptosis, and tumorigenesis. For instance, the mir-17 cluster is overexpressed in B-cell lymphomas and promotes oncogenesis. Conversely, let-7 miRNAs act as tumor suppressors by inhibiting oncogenes like RAS. Abnormal miRNA expression is associated with various cancers, including B-cell chronic lymphocytic leukemia (B-CLL), lung cancer, and breast cancer. miRNAs are often located in genomic regions that are frequently amplified, deleted, or rearranged in cancer. Studies have shown that miRNA profiles can distinguish between different cancer subtypes and predict prognosis. MiRNAs with proproliferative and antiapoptotic activity, such as miR-21, promote oncogenesis, while those with antiproliferative and proapoptotic activity, like let-7, act as tumor suppressors. The mir-17 cluster and miR-21 are examples of miRNAs that contribute to cancer progression. Additionally, miRNAs are involved in stem cell maintenance and cell cycle progression, highlighting their importance in both normal and pathological conditions. Understanding miRNA function in cancer is crucial for developing diagnostic and therapeutic strategies. However, identifying the critical targets of miRNAs and their tissue-specific functions remains a challenge. Continued research into miRNA biology will provide insights into cancer mechanisms and potential therapeutic targets.
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