October 6, 2008; Accepted: October 16, 2008 | Anna M. Krichevsky, Galina Gabriely
The article reviews the functions and regulatory mechanisms of microRNA-21 (miR-21) in human diseases, particularly in cancer. MiR-21 is a highly conserved miRNA that has been identified as the most commonly up-regulated miRNA in human brain tumors, glioblastoma, and various other cancers. The review highlights the following key points:
1. **Expression in Cancer and Other Diseases**: MiR-21 is up-regulated in multiple types of cancers, including breast, colon, lung, pancreas, prostate, stomach, hepatocellular carcinoma, gastric cancer, ovarian cancer, cervical carcinoma, and multiple head and neck cancers. It is also overexpressed in leukemic cancers and viral infections.
2. **Mechanisms of Elevation in Cancer**: MiR-21 expression is regulated at both transcriptional and post-transcriptional levels. Transcriptional control involves the activation of the miR-21 promoter by factors like AP-1 and STAT3. Post-transcriptional regulation includes processing by the Drosha microprocessor complex and maturation by Dicer.
3. **Functions in Cancer**: MiR-21 plays a crucial role in carcinogenesis by regulating multiple genes involved in cell cycle, apoptosis, and invasion. Direct targets include PDCD4, RECK, TPM1, NFIB, and others. MiR-21 promotes tumor growth, survival, and invasion, while its inhibition reduces these processes.
4. **Network and Feedback Regulation**: MiR-21 is involved in positive and negative feedback loops, such as the NFIB-AP-1 loop and the STAT3-IL-6 loop, which contribute to its high expression in cancer.
5. **Biomarker Potential**: MiR-21 is a promising diagnostic and prognostic biomarker due to its strong correlation with advanced stages and poor prognosis in various cancers. It is also detected in circulating exosomes, making it a potential non-invasive biomarker.
The review emphasizes the multifaceted role of miR-21 in disease and its potential as a therapeutic target and biomarker.The article reviews the functions and regulatory mechanisms of microRNA-21 (miR-21) in human diseases, particularly in cancer. MiR-21 is a highly conserved miRNA that has been identified as the most commonly up-regulated miRNA in human brain tumors, glioblastoma, and various other cancers. The review highlights the following key points:
1. **Expression in Cancer and Other Diseases**: MiR-21 is up-regulated in multiple types of cancers, including breast, colon, lung, pancreas, prostate, stomach, hepatocellular carcinoma, gastric cancer, ovarian cancer, cervical carcinoma, and multiple head and neck cancers. It is also overexpressed in leukemic cancers and viral infections.
2. **Mechanisms of Elevation in Cancer**: MiR-21 expression is regulated at both transcriptional and post-transcriptional levels. Transcriptional control involves the activation of the miR-21 promoter by factors like AP-1 and STAT3. Post-transcriptional regulation includes processing by the Drosha microprocessor complex and maturation by Dicer.
3. **Functions in Cancer**: MiR-21 plays a crucial role in carcinogenesis by regulating multiple genes involved in cell cycle, apoptosis, and invasion. Direct targets include PDCD4, RECK, TPM1, NFIB, and others. MiR-21 promotes tumor growth, survival, and invasion, while its inhibition reduces these processes.
4. **Network and Feedback Regulation**: MiR-21 is involved in positive and negative feedback loops, such as the NFIB-AP-1 loop and the STAT3-IL-6 loop, which contribute to its high expression in cancer.
5. **Biomarker Potential**: MiR-21 is a promising diagnostic and prognostic biomarker due to its strong correlation with advanced stages and poor prognosis in various cancers. It is also detected in circulating exosomes, making it a potential non-invasive biomarker.
The review emphasizes the multifaceted role of miR-21 in disease and its potential as a therapeutic target and biomarker.