MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 22 nucleotides in length that regulate gene translation through silencing or degradation of target mRNAs. They are involved in multiple biological processes, including differentiation and proliferation, metabolism, hemostasis, apoptosis or inflammation, and in pathophysiology of many diseases. Numerous studies have suggested circulating miRNAs as promising diagnostic and prognostic biomarkers of many diseases.
The let-7 miRNA family consists of 11 closely related genes. The gene for let-7a is located on the chromosome 22q13.31 and is associated with CpG islands. Let-7a-5p is a microRNA, which inhibits migration, invasion, as well as epithelial-mesenchymal transition by targeting several oncogenes. Moreover, cell proliferation, colony formation, migration and invasion were decreased after induced overexpression of let-7a in breast cancer cells. Deregulation of miR-let-7a-5p is associated with oncological diseases. Thus, miR-let-7a acts as a tumor suppressor and is down-regulated in many types of cancer. Reduced levels of miR-let-7a-5p were reported in lung squamous carcinoma, colorectal cancer, urothelial tumors, lymphoms, breast cancer and many other diagnoses.
Apart from its role in tumor suppression, involvement of miR-let-7a, in cell proliferation pathway in human cells has been reported, and its connection to cerebrovascular and neurodegenerative diseases has been observed. miRNA-let-7a has been shown to directly alter cell cycle progression and proinflammatory cytokine production in brain. In response to inflammation, miR-let-7a participates in reduction of nitrite production and expression of inducible nitric oxide synthase (iNOS) and interleukin-6 and is involved in increased expression of brain-derived inflammatory cytokines in microglia. Thus, miRNA-let-7a could act as a regulator of the function of microglia in inflammation.
- References to let-7a-5p