microRNA-122 Expression Research Articles

MicroRNA-122: assessment of diagnostic significance in HDV infection

Aim: To evaluate the diagnostic significance of the relationship between the level of microRNA-122 expression and liver fibrosis during HDV infection.Materials and methods. The expression of microRNA-122 was determined in 203 blood samples. Blood sampling was done from 53 patients with chronic viral hepatitis D, 49 patients with liver cirrhosis of HDV etiology, and 69 patients with newly diagnosed HBs antigenemia. The control group consisted of practically healthy individuals (n=32).Results. In patients with negative RNA HDV levels, the level of microRNA-122 in the blood serum was significantly higher than in samples with positive RNA HDV levels (14.0±2.8 2^-ΔΔCt and 1.6±0.17 2^-ΔΔCt) (p ˂ 0.005). Meanwhile, in healthy individuals, the expression of microRNA-122 was statistically significantly lower – 1.3±0.03 2^-ΔΔCt (p ˂ 0.005). Undetectable levels of HDV RNA in the serum were accompanied by a high HBV viral load and a significantly higher level of microRNA-122, which was 8.7 times higher than in the group of HDV RNA-positive patients (p<0.005). In patients with liver fibrosis F1, the expression of microRNA-122 was higher than in patients with liver fibrosis F2, F3, F4 (p = 0.0001). The lowest levels of microRNA-122 were observed in liver fibrosis F4. Conclusion. The expression level of microRNA-122 in blood serum during HDV infection decreases as liver fibrosis progresses. The development of cirrhosis is accompanied by a 3.7-fold drop in the level of microRNA-122 compared to the group of patients with chronic hepatitis D. MicroRNA-122 can be used in laboratory monitoring of patients with various stages of HDV infection as an indicator of the activity of the process, assessing the severity of liver damage and the rate of progression of liver fibrosis.> ˂ 0.005). In patients with liver fibrosis F1, the expression of microRNA-122 was higher than in patients with liver fibrosis F2, F3, F4 (p = 0.0001). The lowest levels of microRNA-122 were observed in liver fibrosis F4.Conclusion. The expression level of microRNA-122 in blood serum during HDV infection decreases as liver fibrosis progresses. The development of cirrhosis is accompanied by a 3.7-fold drop in the level of microRNA-122 compared to the group of patients with chronic hepatitis D. MicroRNA-122 can be used in laboratory monitoring of patients with various stages of HDV infection as an indicator of the activity of the process, assessing the severity of liver damage and the rate of progression of liver fibrosis.

Analyzing the Expression of MicroRNA-375 and its Target Gene p53 in Oral Squamous Cell Carcinoma and its Implication in Oral Carcinogenesis

Objective: Oral mucosal cancers are the 11th most common human malignancies worldwide with a five-year survival rate of ≤50%. The lacunae of reliable diagnostic and prognostic markers pose an enormous challenge to the timely identification and prediction of disease progression in oral cancer. MicroRNAs (miRNAs) are emerging molecular markers associated with cancer initiation, progression, and therapy. The present study evaluated the microRNA -375(miR-375) expression and its target p53 gene in Oral squamous cell carcinoma (OSCC) to validate its utility as a diagnostic marker of the disease. Patients and Methods: This case-control study targeted histopathologically diagnosed cases of OSCC. miR-375 was quantified from 22 cases of OSCC and corresponding control tissues using qRT-PCR. Mutant p53 expression in cases and controls was determined by subjecting the tissues to immunohistochemical Results: Significant downregulation of miR-375 was noted in OSCC tissues (68.1%) compared to the control tissues with a mean fold change of 83.9 (p<0.05). Significant downregulation of miR-375 was noted in Paan and tobacco chewing patients (77.8%). Men exhibited considerable downregulation compared to women (p<0.05). The miR-375 expression levels did not correlate with the patient’s age, location, size, nodal status, and histopathological grade of the tumor. About 63.6 % of OSCC tissues showed mutant p53 positivity. Mutant p53 expression was noted in 73.3% of miR-375 downregulated tumors. Smokers exhibited higher expression of mutant p53 contrary to non-smokers(p<0.00). P53 immunopositivity showed a correlation with tumor size, histopathological grade, and nodal metastasis. Conclusion: The findings of the study indicate that miR-375 downregulation may have a crucial effect on oral carcinogenesis by targeting p53. miR-375 should be further evaluated as a potential marker for oral cancer diagnosis.

Correlation between serum microRNA-122 and VEGF expression and pregnancy outcome in gestational diabetes mellitus patients.

Gestational diabetes mellitus (GDM) seriously influences the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, our study planned to probe the correlation between serum microRNA-122 and VEGF expression and pregnancy outcome in GDM patients. This was a retrospective study of the correlation between serum microRNA-122 and vascular endothelial growth factor (VEGF) expression and pregnancy outcome in GDM patients. Sixty GDM patients admitted to the Fourth Hospital of Shijiazhuang from January 2021 to October 2022 were included in the research group (RG), and another 60 healthy pregnant women were included in the control group (CG). Serum miR-122 and VEGF levels were quantified using quantitative real-time polymerase chain reaction. The value of miR-122 and VEGF in predicting adverse pregnancy outcomes was analyzed by receiver operating characteristic curve. Serum miR-122 and VEGF levels in the RG were higher relative to the CG. The total occurrence of adverse pregnancy outcomes in the RG was higher relative to the CG (P<0.05). Serum miR-122 together with VEGF levels in the poor outcome group was higher relative to the good outcome group (P<0.05). ROC analysis revealed that miR-122 and VEGF could be used to predict adverse pregnancy outcome (P<0.0001). The area under the curve of miR-122 was 0.860, 95% confidence interval (CI) =0.793-0.926, and the area under the curve of VEGF was 0.780, 95% CI =0.694-0.866. Serum levels of miR-122, VEGF were positively related with abortion, preterm delivery, low birth weight infants, macrogenesis infants, and fetal development abnormalities (P<0.001). The higher serum miR-122 and VEGF levels in GDM patients with satisfactory blood glucose control, the greater the probability of adverse pregnancy outcome, which should be paid attention to by clinicians.

Optimized thyroid transcription factor-1 core promoter-driven microRNA-7 expression effectively inhibits the growth of human non-small-cell lung cancer cells.

Targeted gene therapy has become a promising approach for lung cancer treatment. In our previous work, we reported that the targeted expression of microRNA-7 (miR-7) operated by thyroid transcription factor-1 (TTF-1) promoter inhibited the growth of human lung cancer cells in vitro and in vivo; however, the intervention efficiency needed to be further improved. In this study, we identified the core promoter of TTF-1 (from -1299 bp to -871 bp) by 5' deletion assay and screened out the putative transcription factors nuclear factor-1 (NF-1) and activator protein-1 (AP-1). Further analysis revealed that the expression level of NF-1, but not AP-1, was positively connected with the activation of TTF-1 core promoter in human non-small-cell lung cancer (NSCLC) cells. Moreover, the silencing of NF-1 could reduce the expression level of miR-7 operated by TTF-1 core promoter. Of note, we optimized four distinct sequences to form additional NF-1-binding sites (TGGCA) in the sequence of TTF-1 core promoter (termed as optTTF-1 promoter), and verified the binding efficiency of NF-1 on the optTTF-1 promoter by electrophoretic mobility shift assay (EMSA). As expected, the optTTF-1 promoter could more effectively drive miR-7 expression and inhibit the growth of human NSCLC cells in vitro, accompanied by a reduced transduction of NADH dehydrogenase (ubiquinone) 1α subcomplex 4 (NDUFA4)/protein kinase B (Akt) pathway. Consistently, optTTF-1 promoter-driven miR-7 expression could also effectively abrogate the growth and metastasis of tumor cells in a murine xenograft model of human NSCLC. Finally, no significant changes were detected in the biological indicators or the histology of some important tissues and organs, including heart, liver, and spleen. On the whole, our study revealed that the optimized TTF-1 promoter could more effectively operate miR-7 to influence the growth of human NSCLC cells, providing a new basis for the development of microRNA-based targeting gene therapy against clinical lung cancer.

Liver Graft MicroRNAs Expression in Different Etiology of Acute Jaundice after Living Donor Liver Transplantation.

Simple SummaryAcute jaundice, a critical problem after living donor liver transplantation, often required efforts to discriminate its etiologies. MicroRNAs are small non-coding RNAs, which express differently during disease development. To differentiate the etiology of acute jaundice after living donor liver transplantation, we examined hepatic microRNA expression patterns in several liver graft pathologies. Eighty liver transplant recipients undergoing post-transplant liver graft biopsy for the evaluation of acute jaundice were enrolled in this one-year prospective study. Using real-time quantitative reverse transcription-polymerase chain reaction profiling assay, we identified intra-graft microRNA (microRNA-122, microRNA-301, microRNA-133a, and microRNA-21) signatures in various allograft pathologies (37 recipients with acute cholangitis, 20 recipients with acute rejection, 12 recipients with recurrent hepatitis, 6 recipients with non-specific pathological change and 5 recipients with fatty change). In acute cholangitis, intra-graft microRNA-122, microRNA-301, and microRNA-21 significantly down-regulated; in acute rejection, intra-graft microRNA-122 significantly up-regulated and intra-graft microRNA-133a significantly down-regulated; in recurrent hepatitis, intra-graft microRNA-122, microRNA-301, and microRNA-21 remarkably up-regulated; and in fatty change, only intra-graft microRNA-133a up-regulated in significance. Our study suggests that specific intra-graft microRNA expression patterns as a checklist may be helpful for differential diagnosis of acute jaundice etiologies following living donor liver transplantation.Background: Acute jaundice remains a critical problem following liver transplantation. MicroRNAs (miRNAs) are involved in regulating gene expression related to various disease phenotypes and statuses. Aims: To differentiate acute jaundice etiology after living donor liver transplantation (LDLT), we examined the hepatic miRNA expression patterns in several liver graft pathologies. Methods: Eighty liver transplant recipients undergoing post-LDLT graft biopsy for the evaluation of acute jaundice were enrolled in this 1-year prospective study. Using a real-time quantitative reverse transcription-polymerase chain reaction profiling assay, we identified hepatic miRNA (miRNA-122, miRNA-301, miRNA-133a, and miRNA-21) signatures in various allografts pathologies. Results: Pathologic findings of the 80 recipients were as follows: acute cholangitis (AC), 37 (46%); acute rejection (AR), 20 (25%); recurrent hepatitis (RH), 12 (15%); non-specific pathological change, 6 (8%); and fatty change (FC), 5 (6%). None of these identified hepatic miRNAs expression pattern was significantly correlated with serum parameters, including neutrophil-lymphocyte ratio. In AC, hepatic miRNA-122, miRNA-301, miRNA-133a, and miRNA-21 expression was significantly downregulated (p < 0.05). MicroRNA-122 expression was elevated in cases of AR and RH (p < 0.05); miRNA-301 and miRNA-21 expression was higher in RH than in AC (p < 0.05); and miRNA-133a expression was higher in FC than in AR (p < 0.05). Conclusions: Our study suggests that specific hepatic miRNA expression patterns as a checklist may be useful for differential diagnosis of acute jaundice following liver transplantation.

Expression of Concern: "Luteolin alleviates LPS-induced bronchopneumonia injury in vitro and in vivo by down-regulating microRNA-132 expression" [Biomedicine & Pharmacotherapy 106 (2018) 1641-1649

Expression of Concern: "Luteolin alleviates LPS-induced bronchopneumonia injury in vitro and in vivo by down-regulating microRNA-132 expression" [Biomedicine & Pharmacotherapy 106 (2018) 1641-1649

MicroRNA-127 and MicroRNA-132 Expression in Patients with Methamphetamine Abuse in East Azerbaijan, Iran: A Case-Control Study.

Addiction is a personal and social problem worldwide, and has physical and psychological effects on consumers' health. Recently, miRNAs have been described as noninvasive biomarkers. Currently, methamphetamine abuse (MA) is mainly diagnosed by chromatography. This study aimed to investigate the expression and diagnostic value of miR-127 and miR-132 in blood samples of patients with MA and non-user healthy controls. A total of 60 patients with MA (case group) and 60 non-user healthy individuals (control group) were selected from Tabriz, East Azerbaijan, Iran. Peripheral blood was obtained and total RNA was extracted. Then, cDNA synthesis was performed and miR-127 and miR-132 expression was evaluated using real time polymerase chain reaction (PCR) method. The results of this study demonstrated that miR-127 was significantly lower (0.042-fold change) in patients with MA than in the control group (P<0.05). However, miR-132 was significantly higher (7.1-fold change) in patients with MA than in the control group (P<0.05). In general, expression of miR-127 and miR-132 may alter in patients with MA. Further studies are needed to identify underlying molecular mechanisms in patients with MA.

Association of Depression With Cardiovascular Diseases.

Depression has long been associated with cardiovascular morbidity and mortality. We have reviewed the various factors (hormonal, inflammatory, neuroimmune, and behavioral) involved in depression and associated cardiovascular risk factors. Elevation of glucocorticoids due to activation of the hypothalamic-pituitary-adrenal (HPA) axis in chronic stress of depression results in hyperglycemia, causing insulin resistance, which is a risk factor for heart diseases. This increase in glucocorticoids also stimulates the production of pro-inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha. Literature also showed that chronic stress in depression activates platelet receptors resulting in endothelial dysfunction and cardiovascular morbidity. It has been shown by various studies that depressed patients are more prone to unhealthy lifestyles like eating more processed food, physical inactivity, smoking, and alcohol consumption resulting in weight gain and insulin resistance. Further in the literature, we reviewed some genetic factors associated with depression and cardiovascular outcomes. Elevated glucocorticoids reduce brain-derived neurotrophic factor-dependent upregulation of glutamate receptors involved in various neural circuits associated with depression and neural diseases by suppressing microRNA-132 expression. In depressed obese patients, proprotein convertase subtilisin/kexin type 9 (PCSK-9), a regulator of low-density lipoprotein cholesterol, has been shown to be associated with insulin resistance. This review sheds light on the importance of diagnostic, preventive, and treatment strategies in depressed patients to reduce overall cardiovascular morbidity and mortality.

Pediatric Extracranial Germ Cell Tumors: Expression of microRNA.

Germ cell tumors (GCTs) may occur from the neonatal period to late adulthood, characterized by extensive clinical and pathologic heterogeneity. MicroRNAs are a family of small noncoding RNAs that regulate a wide array of biological processes including carcinogenesis. MicroRNAs may be used for many purposes in clinical diagnostics. Numerous studies have proven the diagnostic value of microRNA371-373 and microRNA302/367 expression in malignant GCT. The diagnostic value of microRNA375 is disputable, because while its value is confirmed by some research data, there are still others denying it. The results of our own research on the relative expression of 10 microRNAs, including microRNA375, associated with GCT in the tumor tissues of 84 children and adolescents are presented. In our research, overexpression of microRNA 371-373, 302/367 detected in the group of malignant GCT subtypes. Statistically significant expression of microRNA375 have been defined not only in the group of malignant GCT subtypes, but also in the group of immature teratomas. Among malignant GCTs, high expression of microRNA375 is specific for yolk sac tumors. In the group of seminomas, embryonic carcinomas, and mature teratomas expression of microRNA375 was observed imperceptible, even so the results were statistically insignificant. Expression of microRNA 371-373, 302/367 is representative of malignant GCT subtypes. Statistically significant and high expression of microRNA375 attributable for yolk sac tumors and immature teratomas.

MicroRNA-132 promotes atherosclerosis by inducing mitochondrial oxidative stressmediated ferroptosis

To explore the expression of microRNA-132 (miR-132) and its potential role in the development of atherosclerosis (AS). Thirty AS samples and 30 samples of normal peripheral vessels were collected from atherosclerotic patients undergoing peripheral angiostomy in our hospital for detecting the expression level of miR-132 using RT-qPCR. The expression of miR-132 in human umbilical vein endothelial cells (HUVEC) was up-regulated by liposome transfection, and intracellular reactive oxygen species (ROS), localization relationship between ROS and mitochondria, functional changes of mitochondrial reactive oxygen superoxide species (mtROS), mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were analyzed by flow cytometry and laser confocal microscopy. The activity of mitochondrial redox respiratory chain complex (type I, II, III, IV and V) in HUVECs was detected using ELISA, and the expression levels of key iron death proteins were detected with Western blotting. RT-qPCR results showed that miR-132 was significantly up-regulated in atherosclerotic plaques compared with normal vascular samples (P < 0.001). Compared with control HUVECs, HUVECs overexpressing miR-132 showed a significantly increased level of intracellular ROS (P < 0.001), and most of ROS was colocalized with mitochondria. HUVECs overexpressing miR-132 also showed significantly decreased MMP (P < 0.001) and obviously increased mtROS (P < 0.001) and opening of mPTP (P < 0.001), which led to mitochondrial REDOX respiratory chain stress disorder. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001). MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for AS.

Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis.

The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis. The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups. This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed. SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls (p<0.01) and increased in LN more than non-LN group (p<0.001). SOX2 significantly decreased in patient groups compared to controls (p<0.001), and was more in LN compared to non-LN group (p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups (p<0.001). miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.

Abstract 8879: Circulating Levels of MicroRNA-122 and Hepatic Fat Changes in Response to Lifestyle Intervention: Central Magnetic Resonance Imaging Randomized Controlled Trial

Introduction: Compelling evidence has linked liver-specific microRNA-122 (miR-122) expression with hepatic fat distribution; however, little is known about the relations between changes in circulating miR-122 and liver fat in response to weight-loss interventions. We aimed to prospectively investigate the association between serum miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions. Methods: The CENTRAL trial is an 18-month randomized controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat (LF) diet or a Mediterranean/low-carbohydrate (MED/LC) diet. After six months of dietary intervention, each diet group was further randomized into added physical activity groups (LFPA+, MED/LCPA+) or no added physical activity groups (LFPA-, MED/LCPA-) for the following 12 months of intervention. The current study included 220 participants with repeated measurements on serum miR-122 and hepatic fat content (percentage) over 18 months. Results: In the study participants, serum concentration of miR-122 significantly increased from baseline to 18 months, while no difference was observed across the four intervention groups. We found a significant association between miR-122 and hepatic fat percentage at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content ( P trend&lt;0.001). In addition, we found that a higher elevation in log-transformed miR-122 was associated with a greater reduction in hepatic fat percentage during 18-month interventions, independent of weight loss (β=1.56, P trend=0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months ( P interaction=0.02). The association between changes in miR-122 and hepatic fat content changes appeared to be stronger among participants with higher baseline fasting glucose levels than those with lower levels. Conclusion: Our data indicate that participants with higher serum miR-122 levels may benefit more in reduction of hepatic fat content in response to Mediterranean/low-carbohydrate diet and physical activity interventions.

Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling

Although microRNA-7 (miRNA-7) is known to regulate proliferation of cancer cells by targeting Epidermal growth factor receptor (EGFR/ERBB) family, less is known about its role in cardiac physiology. Transgenic (Tg) mouse with cardiomyocyte-specific overexpression of miRNA-7 was generated to determine its role in cardiac physiology and pathology. Echocardiography on the miRNA-7 Tg mice showed cardiac dilation instead of age-associated physiological cardiac hypertrophy observed in non-Tg control mice. Subjecting miRNA-7 Tg mice to transverse aortic constriction (TAC) resulted in cardiac dilation associated with increased fibrosis bypassing the adaptive cardiac hypertrophic response to TAC. miRNA-7 expression in cardiomyocytes resulted in significant loss of ERBB2 expression with no changes in ERBB1 (EGFR). Cardiac proteomics in the miRNA-7 Tg mice showed significant reduction in mitochondrial membrane structural proteins compared to NTg reflecting role of miRNA-7 beyond the regulation of EGFR/ERRB in mediating cardiac dilation. Consistently, electron microscopy showed that miRNA-7 Tg hearts had disorganized rounded mitochondria that was associated with mitochondrial dysfunction. These findings show that expression of miRNA-7 in the cardiomyocytes results in cardiac dilation instead of adaptive hypertrophic response during aging or to TAC providing insights on yet to be understood role of miRNA-7 in cardiac function.

Oleanolic acid inhibits the migration and invasion of hepatocellular carcinoma cells by promoting microRNA-122 expression.

MicroRNAs are emerging as important endogenous regulators of gene function and they are playing an important role in the occurrence and development of cancer. They are also regarded as robust biomarkers of cancer diagnosis and prognosis. Hepatocellular carcinoma (HCC) is a common and complex human malignancy with high mortality and morbidity in the world. MicroRNA-122 (miR-122) is a liver-specific microRNA and is closely associated with HCC metastasis, which makes miR-122 a promising target for drug design and development. In this study, we performed a cell-based screening method for discovering miR-122 activators and found that oleanolic acid (OA), a natural pentacyclic triterpene, specifically increased miR-122 expression in a concentration-dependent manner. Two HCC cell lines (HepG2 and Sk-hep-1 cells) were used to evaluate the effect of OA on cell migration and invasion abilities. The results indicated that OA attenuated the migration and invasion abilities of HCC cells by upregulating miR-122 expression. In addition, OA increased the expression of E-cadherin and decreased the expression of β-catenin, N-cadherin and vimentin. After knocking down miR-122 with miR-122 inhibitor, we found that the effect of OA on these epithelial-to-mesenchymal transition (EMT) related molecules was significantly weakened, indicating OA exhibited anti-EMT effect by increasing the expression of miR-122. These finding may help to better understand the molecular mechanism of OA's anti-metastasis activity.

Inhibition of microRNA turns back the CLOCK of hair follicle aging.

A new study shows that increased microRNA-31 expression is associated with hair follicle aging. Genetic deletion of the microRNA or pharmacological inhibition of its downstream effectors suppresses hair follicle stem cell aging in mice.

Analysis of Serum MicroRNA-122 Expression at Different Stages of Chronic Hepatitis B Virus Infection.

Objective To investigate the expression of microRNA-122 (miR-122) in the progression of chronic hepatitis B virus- (HBV-) infected liver diseases, thus determining the role of serum miR-122 as a marker of HBV-caused liver injury. Methods Sera were collected from patients with different stages of HBV infection (n = 63) and healthy volunteers (n = 11). And the serum miR-122 levels were detected using RT-qPCR. Moreover, an analysis was applied for identifying the specific correlation of the miR-122 level with HBV DNA, HBeAg, and ALT levels. After liver biopsy, Ishak scoring was utilized for evaluation of the fibrosis stage and the histological activity index (HAI). Results We confirmed, in the serum, increased miR-122 expression in HBV-infected patients and its highest expression in chronic HBV carriers, based on such comparison between the healthy controls and patients. The correlation analysis results were taken as confirmation of the positive relationship of miR-122 with HBV DNA (r = 0.354, P = 0.005) and ALT (r = 0.331, P = 0.009). But no correlation of this molecule with HBeAg levels was found (P = 0.187). In comparison with the HBeAg-negative patients, serum miR-122 expression showed an increase in the HBeAg-positive patients (P = 0.001). miR-122 expression, in addition, was of a significant correlation with HAI, but not with the liver fibrosis score. Conclusion The peak of the serum miR-122 expression normally occurs in the early stage of the progression from the HBV carrier phase to chronic hepatitis to cirrhosis. This molecule can be considered as a marker for evaluation of HBV-caused liver injury.

Over-Expression of MicroRNA-122 Inhibits Proliferation and Induces Apoptosis in Colon Cancer Cells.

MicroRNA, a non-coding RNA molecule plays a vital role in post transcriptional gene expression. MicroRNA-122, a liver specific microRNA was found to be downregulated in liver cancer and is associated with hepatocarcinogenesis. Being confirmed as tumor suppressor microRNA in liver carcinogenesis, we aimed to study the expression of microRNA-122 in colon cancer cell lines and the role of microRNA-122 in cell proliferation, invasion and migration of colon cancer cells. The expression of microRNA-122 is quantified using qRT-PCR by TaqMan universal primers. Colon cancer cell lines (SW480, SW620, HCT116) were transfected with microRNA-122 mimic and further studied for determining cell proliferation using CCK-8 kit, migration using Scratch assay, invasion using Transwell assay, apoptosis using Annexin-V FITC kit, and also gene expression. Gene expression results displayed decreased expression of microRNA-122 in colon cancer cell lines. Transfection with microRNA-122 mimics impaired the cell proliferation and migration compared with control. FACS analysis confirmed that the percentage of microRNA-122 mimic transfected cells undergoing early apoptosis was increased. Gene expression of AEG-1, PI3K, CDK6, and PCNA were found to be downregulated in microRNA-122 overexpressed cells. Migratory and invasion potential of transfected cells was lessened in mimic transfected cells compared to control. The overexpression of microRNA-122 inhibited the cellular proliferation, migration, invasion and increased percentage of cells undergoing early apoptosis, suggesting its anti-cancer potential. Studying the role of microRNA-122 and its interactions with oncogenes might pave the way to understand the underlying mechanism in colon cancer.

Protective effect of swimming and genistein on the expression of microRNA 132, insulin growth factor 1, and brain-derived neurotrophic factor genes, as well as spatial memory, in the hippocampus of diabetic ovariectomized rats

Background and Objective: The present study aimed to assess the effects of the combined use of exercise and genistein on the hippocampal expression of microRNA-132, IGF-1, and BDNF in type 2 diabetic ovariectomized rats. Materials and Methods: Wistar female rats in the weight range of 180-220 gr (n=10) were assigned to six groups: sham, ovariectomy, ovariectomized diabetic, ovariectomized diabetic treated with genistein for eight weeks, diabetic ovariectomized treated with swimming for eight weeks, and a group that was treated with both genistein and swimming for eight weeks. The effect of those treatments was assessed by the determination of microRNA-132, insulin growth factor 1 (IGF-1), and brain-derived neurotrophic factor (BDNF) expression levels within the hippocampus. These genes were evaluated by real-time-polymerase chain reaction (RT-PCR) and spatial memory was assessed by the Morris water maze. Results: Ovariectomy demonstrated a decrease in the expression of microRNA-132, IGF-1, and BDNF in the hippocampus, as well as spatial memory, in diabetic ovariectomized rats, which showed a greater reduction in the expression of those genes in rats (P&lt;0.05). Nevertheless, genistein administration, swimming training, and a combination of them significantly up-regulated microRNA-132, BDNF, and IGF-1 expression, as well as spatial memory (P&lt;0.05). Conclusions: As evidenced by the obtained results, the combined use of genistein and swimming could prevent estrogen deficiency effects in the hippocampus of ovariectomized diabetic rats

Effect of microRNA-7 on proliferation, invasion, migration and EMT of hepatoma cell line SMMC-7721.

This study aimed to observe the effect of microRNA-7 on the proliferation and migration of human hepatocellular carcinoma cell line SMMC-7721 and its effect on epithelial-mesenchymal transition (EMT). Eukaryotic expression vector pcDNA3.1(-)-pri-miR-7(p-miR-7) was used to instantaneously transfect human liver cancer cells of SMMC-7721 cells in vitro. The expression of microRNA-7 was detected by RT-qPCR. Western blot was used to detect the expression of EMT marker proteins E-cadherin, β-catenin, N-cadherin and Vimentin. The proliferation of SMMC-7721 cells was detected by CCK-8 assay, and the invasion and migration ability of cells was detected by transwell assay. Compared with the normal group, the expressions of E-cadherin and β-catenin in SMMC-7721 cells transfected with miR-7 were significantly increased (p<0.05), while the expressions of N-cadherin and Vimentin were significantly decreased (p<0.05). Meanwhile, the proliferation, invasion and migration ability of the cells were significantly weakened (p<0.05). The miR-7 can inhibit the proliferation and invasion of human hepatocellular carcinoma cell line SMMC-7721, and its mechanism may be related to upregulation of E-cadherin, β-catenin protein, and downregulation of N-cadherin and Vimentin proteins.

Long-chain non-coding RNA LOC554202 promotes proliferation, migration, and invasion of nasopharyngeal carcinoma cells by binding to microRNA-31 expression and regulating RhoA expression.

Long-chain non-coding LOC554202, as a host gene for microRNA-31, has been shown to play a crucial role in a variety of diseases, especially tumors. However, its biological function in nasopharyngeal carcinoma (NPC) has not been reported. The expression levels of LOC554202 and microRNA-31 in NPC tumor tissue samples and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The impacts of LOC554202 and microRNA-31 on the biological functions of NPC cells were examined by Cell Counting Kit-8 (CCK-8) and transwell assays. In addition, the modulation of LOC554202 on the expressions of microRNA-31 and RhoA was further confirmed by qRT-PCR and Western blot analysis. The data of this study indicated that LOC554202 expression in NPC tissues and cell lines was remarkably upregulated, while microRNA-31 level showed an opposite tendency. Increasing LOC554202 expression remarkably enhanced the growth and metastasis of NPC cells, which was inhibited by overexpression of microRNA-31. Overexpression of LOC554202 downregulated microRNA-31 expression but upregulated that of RhoA, which may be a potential mechanism for the implication of LOC554202 in NPC. As a host gene of microRNA-31, LOC554202 enhances RhoA expression and thus promotes the proliferative capacity and invasiveness of NPC cells.