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 the pathophysiology of many diseases. Numerous studies have suggested circulating miRNAs as promising diagnostic and prognostic biomarkers of many diseases.
Among different types of miRNAs in liver, miR-122 is the most abundant and tissue-specific miRNA. Levels of hsa-miR-122-5p and hsa-miR-885-5p were up-regulated in individuals with fatty liver (FL). Together hsa-miR-122-5p and has-miR-885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels correlated with small VLDL, LDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels correlated inversely with XL HDL cholesterol levels. hsa-miR-122 exhibited significantly different expression levels between fibrosis stages. hsa-miR-122-5p, hsa-miR-146a, hsa-miR-29c and hsa-miR-223 were positively correlated with fibrosis stage. On the contrary, hsa-miR-122-5p and hsa-miR-381-3p were negatively correlated with alanine aminotransferase, aspartate transaminase and HBV viral DNA load. Liver biopsies showed that miR-122 is up-regulated in hepatosteatosis. Surprisingly, the protein and RNA level of identified targets of miR-122 are also up-regulated in clinical samples, probably as a disproportionate feedback response to the high level of miR-122. miR-122 might regulate TAG metabolism by targeting key enzymes that are involved in its production pathway. A systematic computational analysis of putative targets of miR-122 identified CTDNEP1 and LPIN1 genes in the triacylglycerol (TAG) pathway.
miR-122-5p overexpression significantly restrained the proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells. The expression levels of miR-122-5p were significantly higher in alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) patients than in non-AFPGC patients. In tissue samples, miR-122-5p expression level tended to be lower in non-AFPGC tissue than the normal gastric mucosa. Conversely, miR-122-5p expression level was significantly higher in AFPGC tissue than both normal gastric mucosa and non-AFPGC tissue samples. Plasma miR-122-5p expression levels were also significantly higher in AFPGC patients than the health volunteers and non-AFPGC patients and were strongly correlated with plasma AFP levels. Moreover, the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in AFPGC patients. In contrast, no correlation was found between miR-122-5p expression levels and liver metastasis in non-AFPGC patients.
In a study of hospital patients who suffered out-of-hospital cardiac arrest, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission. Plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. Event-free survival was significantly worse in patients (patients treated with primary angioplasty) with a higher miR-122-5p/133b ratio, having almost a 9-fold higher risk of death or myocardial infarction and a 4-fold higher risk of adverse cardiovascular events. The miR-122-5p/133b ratio is a new prognostic biomarker for the early identification of STEMI patients at a higher risk of developing major adverse events after undergoing primary percutaneous coronary intervention. Plasma miR-122-5p levels were significantly elevated in AMI patients, while plasma miR-22-5p levels were significantly decreased. In addition, signif
- References to miR-122-5p