Introduction: MicroRNAs (miRNAs) are small non coding regions in RNAs of 20–22 nucleotides, which play an important role in all biological pathways in multicellular organisms including mammals that regulate gene expression at the post transcriptional level. They play a critical role in various cellular processes, including cell development, differentiation, and proliferation. However, dysregulation of miRNA expression or function can contribute to the development and progression of cancer.
In cancer, miRNAs can act as oncogenes or tumor suppressors, depending on their targets and cellular context. Oncogenic miRNAs, also known as oncomiRs, are upregulated in cancer and promote tumorigenesis by repressing tumor suppressor genes or promoting cancer-associated processes such as cell proliferation, invasion, and metastasis. On the other hand, tumor suppressor miRNAs are downregulated in cancer and help maintain genomic stability, inhibit tumor growth, and induce apoptosis.
The dysregulation of miRNAs in cancer can occur through various mechanisms, including genetic alterations, epigenetic modifications, and aberrant processing or maturation. Changes in miRNA expression patterns have been observed in virtually all types of cancer, and specific miRNAs have been implicated in the development, progression, and response to therapy in various cancer types, including breast, lung, prostate, colon, and ovarian cancer.
MiRNAs have also been investigated as biomarkers for cancer diagnosis, prognosis, and prediction of therapeutic response. Their small size, stability in different biological fluids, and tissue-specific expression patterns make them attractive candidates for cancer biomarker development. Additionally, the ability to modulate miRNA expression and function holds promise for the development of miRNA-based therapies for cancer treatment.
In summary, microRNAs play a crucial role in cancer biology by regulating gene expression and cellular processes. Dysregulation of miRNA expression or function can contribute to tumorigenesis and progression, making miRNAs attractive targets for cancer diagnosis, prognosis, and therapy
Methods: 1. Identification of differentially expressed microRNAs: This method involves comparing the expression levels of microRNAs in cancer tissues with that of normal tissues using techniques like microarray analysis or next-generation sequencing.
2. Validation of differentially expressed microRNAs: Once differentially expressed microRNAs are identified, their expression levels are validated in a larger cohort of cancer patients using quantitative PCR or fluorescence in situ hybridization (FISH).
3. Target prediction and pathway analysis: Bioinformatics tools are used to predict potential target genes of the differentially expressed microRNAs. Pathway analysis is then conducted to determine the biological pathways and processes affected by these target genes.
4. Animal models and xenograft assays: Animal models, such as transgenic mice or xenograft models, are used to study the impact of specific microRNAs on cancer development, progression, and response to therapy.
5. Functional rescue experiments: To establish the direct functional relevance of specific microRNAs, experiments involving the rescue of microRNA-mediated phenotypes are performed. This can involve the introduction of a synthetic microRNA mimic or the restoration of target gene expression in the presence of a cancer-associated microRNA.
6. Therapeutic targeting of microRNAs: Based on the findings from the above experiments, therapeutic strategies targeting specific microRNAs can be developed. This can involve the use of antisense oligonucleotides (anti-miRs) to inhibit the oncogenic microRNAs or the use of synthetic mimics to restore the function of tumor-suppressive microRNAs.
7. Biomarker development: Lastly, selected microRNAs may be evaluated as potential biomarkers for cancer diagnosis, prognosis, or prediction of therapeutic response. This can involve developing sensitive and specific assays for their detection in patient samples, such as serum or plasma
Results: Researchers are focusing on the examination of body fluids such as plasma, serum, urine and saliva to determine the circulating levels of miRNAs and to evaluate if they can be used as diagnostic, prognostic and predictive biomarkers in cancer. Such studies have attracted a great deal of attention because of minimally invasive processes to examine miRNA using qPCR. In the serum of prostate cancer patients, the expression levels of pre-selected oncogenic miR-26a, miR-195 and let-7i were shown to be up-regulated compared to those in individuals with benign prostate hyperplasia (BPH) . Similarly, the prognostic value of increased expression levels of circulating miR-141 and miR-375 correlating with low-risk through high-risk and from localized to metastatic prostate cancer was documented . The signature miRNAs, miR-28-3p, miR-30c, miR-92a, miR-140-5p, miR-451 and miR660 in the plasma were found to be deregulated 1–2 years prior to diagnosis of lung cancer and thus, indicated their use in prediction as well as diagnosis . miR-27b, miR-158a, miR-326 signature or miR-200c in the serum of colon cancer patients were found to be useful to identify metastatic tumors . The miR-125b and miR-155 levels in the serum of breast cancer patients were found to be useful for diagnosis, assessing chemotherapeutic response as well as in prognosis . Until recently, miRNA analyses were performed using qRT-PCR and microarray-based approaches. NGS is now emerging as a cost-effective option while bioinformatics analyses are no longer a major problem for continued usage
Conclusion: So far, there have been significant scientific research findings indicating the utility of miRNAs as biomarkers for prediction, diagnosis and prognosis. Evidence is also emerging suggesting that inhibition of oncogenic miRNAs or substitution of tumor suppressive miRNAs could be used to develop novel treatment strategies. The extensive information thus far available in the peer-reviewed scientific publications has been extremely useful to provide guidance for further investigations. Comprehensive, carefully designed, multi-centered, retrospective and prospective studies involving large cohorts in the same and independent laboratories/clinics comparing and validating the data within a similar type of cancer are warranted. Besides, investigations using minimally invasive methods to collect blood, saliva and urine are extremely important for the development of reliable and cost-effective miRNA-based technology for routine use in the clinics for early cancer diagnosis/detection and therapeutic assessment/prognosis.
Keywords: cancer . miRNA . diagnosis . Involvement