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.
In the human genome, miR-451a is encoded in proximity to miR-144 in chromosome region 17q11.2 and its biogenesis occurs via a non-canonical pathway that depends on Ago2 protein. Many studies have established that miR-451a is widely dysregulated in human malignancies, including papillary thyroid carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, gastric cancer, breast cancer, glioma and cutaneous basal cell carcinoma. Serum exosomal miR-451a has diagnostic utility in diffuse large B-cell lymphoma and hepatocellular carcinoma. Furthermore, miR-451a was downregulated in non-small cell lung cancer (NSCLC) tissues and lung cancer cells.
MicroRNA-451a is a cell metabolism-related miRNA. In glioma cells, miR‐451a can regulate glucose transporters such as GLUT1 on the cell membrane to downregulate glucose metabolism and prevent energy supply to cancer cells. In human gastric cancer cells, miR-451a expression was increased by high glucose treatment and decreased significantly when the glucose level was low. It was found that exosomal miR-451a could serve as an indicator of poor prognosis of post-surgery gastric cancer patients and that increased secretion of exosomal miR-451a could be triggered in a low glucose condition.
Besides cancer, miR-451a was reported to be associated with neuronal maturation processes in vitro and in vivo. A regulatory role of miR-451a in brain has been suggested by the studies showing that microparticles derived from cerebrospinal fluid (CSF) of patients in the acute stages of traumatic brain injury (TBI) are specifically enriched in miR-451a. Moreover, miR-451a was identified as a biomarker in pathogenesis and prognosis of acute ischemic stroke (AIS) patients and in transient ischemic attack (TIA) patients. It was also published that miR-451a was downregulated in differentiated myoblasts and the findings suggest an inhibitory role of miR-451a in myogenesis.