Serum miR-21 Research Articles

Exosomal MicroRNA-223, MicroRNA-146, and MicroRNA-21 Profiles and Biochemical Changes in Laryngeal Cancer.

Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers, and its early diagnosis is urgent. Exosomes are believed to have diagnostic significance in cancer. However, the role of serum exosomal microRNAs, miR-223, miR-146, and miR-21, and phosphatase and tensin homologue (PTEN) and hemoglobin subunit delta (HBD) mRNAs in LSCC is unclear. Exosomes were isolated from the blood serum of 10 LSCC patients and 10 healthy controls to perform scanning electron microscopy and liquid chromatography quadrupole time-of-flight mass spectrometry analyses to characterize them and to undergo reverse transcription polymerase chain reaction to identify miR-223, miR-146, miR-21, and PTEN and HBD mRNA expression phenotypes. Biochemical parameters, including serum C-reactive protein (CRP) and vitamin B12, were also obtained. Serum exosomes of 10-140 nm were isolated from LSCC and controls. Serum exosomal miR-223, miR-146, and PTEN were found to be significantly decreased (p < 0.05), in contrast to serum exosomal miRNA-21 (p < 0.01), and serum vitamin B12 and CRP (p < 0.05) were found to be significantly increased, in LSCC vs controls. Our novel data show that the combination of reduced serum exosomal miR-223, miR-146, and miR-21 profiles and biochemical alterations in CRP and vitamin B12 levels may be useful indicators of LSCC that could be validated by large studies. Our findings also suggest a possible negative regulatory effect of miR-21 on PTEN in LSCC, encouraging a more extensive investigation of its role.

Serum miR-21 and miR-29a expression in systemic sclerosis patients.

The aim of our study was to evaluate the expression levels of miR-21 and miR-29a in the serum of systemic sclerosis (SSc) patients and to determine their correlation with clinical and immunological parameters. 34 patients fulfilling the ACR/EULAR 2013 classification criteria for SSc were included in the study. miR-21 and miR-29a expression levels in the serum were determined by PCR (SYBR Green technology). 2-ΔΔCt method was used for analysis. 14 healthy donors were used as controls (HCs). Expression levels of miR-21 were upregulated in the serum of 17 (50.0%) of the patients. The expression of miR-29a was downregulated in 15 (44.12%) of the SSc patients. Receiver operating characteristic (ROC) curve analysis was conducted in order to evaluate the diagnostic accuracy of the expression levels of the studied miRNAs in the serum. Area under the curve (AUC) for miR-21 was 0.634 (95% CI=0.479-0.790), p=0.147 with 64.7% sensitivity and 64.3% specificity. AUC for miR-29a was 0.605 (95% CI=0.420-0.790), with 64.3% sensitivity and 52.9% specificity but without statistical significance (p=0.257). The multimarker analysis of the ROC curves for both miRNAs showed AUC=0.714 (95% CI=0.569-0.860), p=0.021 with 79.4% sensitivity and 42.9% specificity. Levels of miR-29a correlated with the levels of miR-21 in the serum (with Spearman correlation coefficient 0.517, p=0.00017) and with the presence of anti-Scl70 antibodies in the serum (with Spearman correlation coefficient 0.438, p=0.010). Our data showed a deregulation of miR-21 and miR-29a in the serum of patients with SSc which could suggests their potential role in the disease pathogenesis. Further analysis with higher number of patients is needed to confirm if these miRNAs could be used in the clinical practice as diagnostic biomarkers as well as biomarkers for both disease activity and progression.

Abstract 6520: Combination of serum human satellite RNA and miR-21 levels as a biomarker for diagnosis of pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to the difficulty of its diagnosis. Because human satellite II (HSATII) RNA, a satellite repeat RNA, is highly and specifically expressed in human PDAC, the serum HSATII RNA level may be a biomarker for diagnosis of PDAC. To measure the serum HSATII RNA level with high sensitivity and reproducibility, we previously developed a convenient method, tandem repeat amplification by nuclease protection (TRAP) combined with droplet digital PCR (ddPCR). Here, we refined the original method by simultaneously measuring the serum miR-21 level to enhance the detection of PDAC. A total of 135 patients were enrolled in this study, including 65 patients with pancreatic cancer and 70 healthy controls. We developed the PDAC-Index as a combination of the HSATII RNA and miR-21 levels to discriminate PDAC from healthy controls. The PDAC-Index demonstrated good diagnostic performance (AUC: 0.92 (95% CI: 0.86-0.99); sensitivity: 0.94; specificity: 0.85) which was significantly better than HSATII RNA alone (AUC: 0.92 vs 0.82, p=0.004). Importantly, the PDAC-index was elevated in an early-stage PDAC case that was negative for CA19-9. The PDAC-index also discriminated PDAC from chronic pancreatitis and intraductal papillary mucinous neoplasm more accurately than CA19-9. These results suggest that the PDAC-Index may be a promising biomarker for diagnosis of PDAC. Citation Format: Takahiro Seimiya, Takahiro Kishikawa, Mtoyuki Otsuka, Mitsuhiro Fujishiro. Combination of serum human satellite RNA and miR-21 levels as a biomarker for diagnosis of pancreatic cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6520.

Meta-analysis of the characteristic expression of circulating microRNA in type 2 diabetes mellitus with acute ischemic cerebrovascular disease.

To comprehensively evaluate the characteristics of the circulating microRNA expression profile in type 2 diabetic patients with acute ischemic cerebrovascular disease by systematic evaluation and meta-analysis. The literatures up to March 2022 related to circulating microRNA and acute ischemic cerebrovascular disease in type 2 diabetes mellitus were searched and screened from multiple databases. The NOS quality assessment scale was used to evaluate methodological quality. Heterogeneity tests and statistical analyses of all data were performed by Stata 16.0. The differences in microRNA levels between groups were illustrated by the standardized mean difference (SMD) and 95% confidence interval (95% CI). A total of 49 studies on 12 circulating miRNAs were included in this study, including 486 cases of type 2 diabetes complicated with acute ischemic cerebrovascular disease and 855 controls. Compared with the control group (T2DM group), miR-200a, miR-144, and miR-503 were upregulated and positively correlated with acute ischemic cerebrovascular disease in type 2 diabetes mellitus patients. Their comprehensive SMD and 95% CI were 2.71 (1.64~3.77), 5.77 (4.28~7.26) and 0.73 (0.27~1.19), respectively. MiR-126 was downregulated and negatively correlated with acute ischemic cerebrovascular disease in type 2 diabetes mellitus patients, its comprehensive SMD and 95% CI were -3.64 (-5.56~-1.72). In type 2 diabetes mellitus patients with acute ischemic cerebrovascular disease, the expression of serum miR-200a, miR-503, plasma and platelet miR-144 was upregulated and the expression of serum miR-126 was downregulated. It may have diagnostic value in the early identification of type 2 diabetes mellitus with acute ischemic cerebrovascular disease.

Epigenetic Mechanisms and Nephrotic Syndrome: A Systematic Review.

A small subset of people with nephrotic syndrome (NS) have genetically driven disease. However, the disease mechanisms for the remaining majority are unknown. Epigenetic marks are reversible but stable regulators of gene expression with utility as biomarkers and therapeutic targets. We aimed to identify and assess all published human studies of epigenetic mechanisms in NS. PubMed (MEDLINE) and Embase were searched for original research articles examining any epigenetic mechanism in samples collected from people with steroid resistant NS, steroid sensitive NS, focal segmental glomerulosclerosis or minimal change disease. Study quality was assessed by using the Joanna Briggs Institute critical appraisal tools. Forty-nine studies met our inclusion criteria. The majority of these examined micro-RNAs (n = 35, 71%). Study quality was low, with only 23 deemed higher quality, and most of these included fewer than 100 patients and failed to validate findings in a second cohort. However, there were some promising concordant results between the studies; higher levels of serum miR-191 and miR-30c, and urinary miR-23b-3p and miR-30a-5p were observed in NS compared to controls. We have identified that the epigenome, particularly DNA methylation and histone modifications, has been understudied in NS. Large clinical studies, which utilise the latest high-throughput technologies and analytical pipelines, should focus on addressing this critical gap in the literature.

Correlation between miR-21, miR-191 and Clinical Stage of Patients with Diffuse Large B-Cell Lymphoma

To analyze the relationship between microRNA (miR)-21, miR-191 and clinical stage of patients with diffuse large B-cell lymphoma (DLBCL). 100 patients with DLBCL treated in Shanxi Fenyang Hospital from January 2019 to January 2021 were selected as the research subjects. All patients was divided into stage I, stage II, stage III and stage IV according to Ann-Arbor (Cotswolds) staging system at admission. The baseline data of patients at different clinical stages were counted and compared in detail. The relationship between the levels of miR-21 and miR-191 and the clinical stage of DLBCL patients was mainly analyzed. Among the 100 patients with DLBCL, there were 15 patients at stage I, 25 patients at stage II, 37 patients at stage III and 23 patients at stage IV. The levels of miR-21 and miR-191 in patients at stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were increased gradually, which showed statistically significant differences (P<0.05). According to Kendall's tau-b correlation analysis, it was found that the levels of miR-21 and miR-191 were positively correlated with the clinical stage of DLBCL patients (r=0.566, 0.636). Multiple logistic regression analysis showed that the overexpression of serum miR-21 and miR-191 was a risk factor for high clinical stage in patients with DLBCL (OR>1, P<0.05). Bivariate Pearson correlation analysis showed that there was a positive correlation between miR-21 and miR-191 levels in patients with DLBCL (r=0.339). The overexpression of miR-21 and miR-191 in patients with DLBCL is related to high clinical stage.

Circulating microRNAs in gallbladder cancer: Is serum assay of diagnostic value?

The microRNAs (miRNAs) in circulation could serve as biomarkers for cancer detection. Gallbladder carcinoma (GBC) is mostly asymptomatic; therefore, using microRNAs (miRNAs) as an early diagnostic biomarker could be a valuable tool. We aimed to identify the tumor-associated miR-1, miR130, miR-146, miR-182, and miR-21expression in serum as a biomarker for early detection of GBC and identify their possible diagnostic role. The study group comprised of paired serum and tissue samples from 34 GBC, 19 cholecystitis (CC), 21 normal controls (uninflamed gall bladder), and additional 29 serum-only samples of GBC. Total RNA was isolated using a commercially available RNA isolation kit (Applied Biosystem, USA) and reverse transcribed using Advanced Taqman MicroRNA reverse transcription kit. The relative expression of miRNAs was analyzed using Quantitative real-time polymerase chain reaction. The diagnostic potential of these miRNAs was assessed by ROC analysis. In paired samples, the trend towards up and down regulation for miR-182, miR-21, miR-1, miR-130, and miR-146 was similar in both tissue and sera of GBC. The expression pattern of serum miR-1, miR130, and miR-146 gradually decreased from normal control (NC) to CC to GBC, while miR-21 and miR-182 gradually increased from NC to CC to GBC. The miR-1, miR-121, miR-182, and miR-146 significantly differed between CC vs. early stage and early stage vs. NC. Among these miRNAs, the sensitivity of miR-1 (85.71 %) was the highest, and the specificity of miR-21 was the highest (92.73 %). The combined sensitivity for miRNAs ranged from 73.13 % (CI: 60.90-83.24 %) to 98.63 % (CI: 89.0-99.61 %); however, the specificity was lower. In stage I&II vs. III&IV discrimination, the diagnostic sensitivity of miR-1 was highest (89.36 %, CI: 76.90-96.45). The two miRNAs, in combination, increase the diagnostic sensitivity. Circulating serum miRNAs may provide a new approach for clinical application. Panels of specific circulating miRNA, which require further validation, could be potential non-invasive diagnostic biomarkers for GBC in combination with abnormal radio diagnostic scans.

MicroRNA-145 and microRNA-486 are potential serum biomarkers for vascular calcification.

MicroRNAs (miRs) regulate vascular calcification (VC), and their quantification may contribute to suspicion of the presence of VC. The study was performed in four phases. Phase 1: miRs sequencing of rat calcified and non-calcified aortas. Phase 2: miRs with the highest rate of change, plus miR-145 [the most abundant miR in vascular smooth muscle cells (VSMCs)], were validated in aortas and serum from rats with and without VC. Phase 3: the selected miRs were analyzed in epigastric arteries from kidney donors and recipients, and serum samples from general population. Phase 4: VSMCs were exposed to different phosphorus concentrations, and miR-145 and miR-486 were overexpressed to investigate their role in VC. miR-145, miR-122-5p, miR-486 and miR-598-3p decreased in the rat calcified aortas, but only miR-145 and miR-486 were detected in serum. In human epigastric arteries, miR-145 and miR-486 were lower in kidney transplant recipients compared with donors. Both miRs inversely correlated with arterial calcium content and with VC (Kauppila index). In the general population, the severe VC was associated with the lowest serum levels of both miRs. The receiver operating characteristic curve showed that serum miR-145 was a good biomarker of VC. In VSMCs exposed to high phosphorus, calcium content, osteogenic markers (Runx2 and Osterix) increased, and the contractile marker (α-actin), miR-145 and miR-486 decreased. Overexpression of miR-145, and to a lesser extent miR-486, prevented the increase in calcium content induced by high phosphorus, the osteogenic differentiation and the loss of the contractile phenotype. miR-145 and miR-486 regulate the osteogenic differentiation of VSMCs, and their quantification in serum could serve as a marker of VC.

P101 Circulating MicroRNA-16 in Inflammatory Bowel Disease Patients - Potential Biomarker to Assess Inflammation

Abstract Background miR-16 is important for the inflammatory processes and the signal pathways that participate in the immune system regulation. As there is an immune mucosal inflammation in IBD, miR-16 could also serve as a potential biomarker to assess inflammation. Methods The study aims to assess the expression of serum miR-16 in IBD patients and to correlate its expression with clinical parameters such as disease extent, activity and severity. 35 patients with UC and 35 patients with CD were included in the study. Serum miR-16 expression was assessed with reverse transcriptase quantitative real time PCR (RT-qPCR), and was then correlated with the miR-16 levels in a group of 30 healthy subjects. Results miR-16 expression is increased in patients with CD, localized in the small intestine (3.54±2.33) and in pancolitis Е3 of UC (2.01±1.54). There is a significant difference in miR-16 expression in inflammatory (B1), stenotic (B2) and penetrating (B3) form of CD (р=0.010) with higher expression levels in the more severe B2 and B3 forms. There is no significant difference in miR-16 expression according to the forms of evolution in patients with UC. In patients with CD, there is a moderate direct correlation between the expression of miR-16 and the Crohn’s disease activity index CDAI (r=0.424; p=0.015). miR-16 expression levels increase progressively in correlation with the activity of CD. Patients with moderate activity of their CD have significantly higher miR-16 expression (4.27±3.00) as compared to patients with mild activity (2.38±1.06) or in remission (2.41±1.23) of the disease (р=0.048). The increased expression levels of miR-16 are a risk factor for CDAI &amp;gt; 150 levels (OR=4.80 (0.506-45.495); p=0.015). In patients with UC, there is no correlation between the miR-16 expression levels and the severity (S) index, measured as per the Montreal classification or the endoscopic activity, measured as per the Partial Mayo score. In patients with severe disease, measured by both S index (1.38±0.89) and Partial Mayo score (1.80±1.12), there is a decrease in miR-16, close to normal controls. MiR-16 expression levels do not correlate with any treatment that was given in patients with either CD or UC. Conclusion The increased miR-16 serum expression corelates with the localization of CD in the small intestine and the stenotic and penetrating form of the disease. Increased miR-16 levels are also found in extensive UC. In patients with CD there is a positive correlation between the expression of miR-16 and the activity of the disease as measured by the CDAI.

Retracted: Analysis on Value of Applying Serum miR-144 and miR-221 Levels in Diagnosing Atherosclerosis.

[This retracts the article DOI: 10.1155/2022/2261854.].

Increased extracellular release of microRNAs from dorsal root ganglion cells in a rat model of neuropathic pain caused by peripheral nerve injury.

microRNAs (miRNAs) are extracellularly released by cells for intercellular communication, while intracellularly, they inhibit the expression of specific genes. An increasing number of studies suggest that extracellular miRNAs have great potential as both therapeutic targets and disease-specific biomarkers in a variety of diseases, including pain disorders. However, little is known about miRNA release from dorsal root ganglion (DRG) neurons in neuropathic pain caused by peripheral nerve injury. In this study, we investigated the changes in the extracellular release of miRNAs from DRG neurons in a rat model of neuropathic pain induced by chronic constriction injury of the sciatic nerve. We found increased release of six miRNAs (let-7d, miR-21, miR-142-3p, miR-146b, miR-203-3p and miR-221) from primary cultured DRG neurons prepared from rats 7 days after nerve injury. Among these, miR-221 was also increased in serum from days 7 to 28 after nerve injury. In contrast, serum miR-221 levels and its release from DRG neurons were unchanged in an inflammatory pain model produced by intraplantar injection of complete Freund's adjuvant. These results suggest that the increased release of specific miRNAs by DRG neurons may be involved in the pathophysiology of neuropathic pain through extracellular as well as intracellular mechanisms. Furthermore, serum miR-221 may be useful as a biomarker of neuropathic pain caused by peripheral nerve injury.

Retracted: Serum miR-204 and miR-451 Expression and Diagnostic Value in Patients with Pulmonary Artery Hypertension Triggered by Congenital Heart Disease.

[This retracts the article DOI: 10.1155/2022/9430708.].

Clinical Expression Analysis of Serum miR-29b and miR-126 in Patients with Non-Proliferative Diabetic Retinopathy

Clinical Expression Analysis of Serum miR-29b and miR-126 in Patients with Non-Proliferative Diabetic Retinopathy

Correlation of NF-kB Serum Level with the Expression Pattern of Microrna-221 in a Sample of Hcv-Exposed Iraqi Patients

Background: Hepatitis C virus (HCV) has the ability to change cellular messenger RNA transcription and translation by stimulating the synthesis of cellular microRNAs (miRNAs) that impair immune response and facilitate viral reproduction. One of the most important members of the immune response against HCV is nuclear factor-kappa B (NF-κB), which is regulated by cellular miRNAs. Aims: we aimed to investigate the correlation of NF-κB serum level with circulatory miRNA-221 (miR-221) fold change in HCV-exposed individuals. Materials and Methods: Serum level of NF-κB in 88 samples (22 patients with persistent HCV infection, 22 individuals with spontaneous HCV virus clearance, 22 individuals treated with direct-acting antivirals (DAAs) drugs, and 22 uninfected apparently healthy blood donors as control) was measured by enzyme-linked immunosorbent assay. Reverse transcriptase–polymerase chain reaction was used to quantify the expression fold of circulatory miR-221. Results: The results showed that there was a significant decrease in the mean level of NF-κB at P &lt; 0.000 among HCV-exposed patients (2.0058 ng/ml) as compared to the control group (2.9841 ng/ml). The mean fold change of miR-221 was significantly upregulated about six more times among HCV-exposed patients (mean = 6.3545) compared to the control group (mean = 1.1864). Furthermore, the mean ± standard deviation of miR-221 fold change in patients with persistent HCV infection was significantly higher compared to patients cured after DAA therapy (P = 0.048), there was a weak negative correlation (r = −0.246, P = 0.021) between NF-κB serum level and miR-221 folding level. Conclusion: HCV infection disrupts NF-κB activation, resulting in dysregulation of miR-221 that persists long after the virus has been cleared. Thus, quantification of serum NF-κB and miR-221in HCV-exposed patients could be used as noninvasive prognostic marker during long-term follow-up. Furthermore, a miRNAs profile analysis can help distinguish HCV-exposed from healthy individuals.

Retracted: Study on Serum miR-204 Expression Levels in Patients with Severe Pneumonia and Patients with Primary Bronchial Lung Cancer and Its Diagnostic Value.

[This retracts the article DOI: 10.1155/2021/6034413.].

MicroRNA-124 expression in Kupffer cells modulates liver injury by targeting IL-6/STAT3 signaling

MicroRNA-124 (miR-124) is related to liver injury due to chronic hepatitis B (CHB) and hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, the mechanism whereby miR-124 regulates liver inflammation remains unknown. In this study, we show that serum miR-124 serves as a compensatory predictive factor for organ failure and the 28-day prognosis of patients with HBV-ACLF. Moreover, within a mouse model of concanavalin A-induced acute liver injury, miR-124 is highly expressed in Kupffer cells. Overexpression of miR-124 significantly decreases interleukin-6 (IL-6) secretion, and relieves pathological liver necrosis to a great extent. Mechanistically, miR-124 directly targets the 3′-untranslated region of signal transducer and activator of transcription 3 (STAT3) and inhibits IL-6/STAT3 signaling, which reduces pro-inflammatory Kupffer cell polarization. Collectively, our findings suggest that miR-124 can potentially serve as a predictive biomarker for HBV-ACLF prognosis and may represent a promising therapeutic target for relieving severe liver injury resulting from cytokine storms.

Circulating MicroRNAs and Extracellular Vesicle-Derived MicroRNAs as Predictors of Functional Recovery in Ischemic Stroke Patients: A Systematic Review and Meta-Analysis.

Stroke accounts for the second leading cause of death and a major cause of disability, with limited therapeutic strategy in both the acute and chronic phases. Blood-based biomarkers are intensively researched and widely recognized as useful tools to predict the prognoses of patients confronted with therapeutically limited diseases. We performed a systematic review of the circulating biomarkers in IS patients with prognostic value, with a focus on microRNAs and exosomes as predictive biomarkers of motor and cognitive recovery. We identified 63 studies, totalizing 72 circulating biomarkers with prognostic value in stroke recovery, as follows: 68 miRNAs and exosomal-miRNAs being identified as predictive for motor recovery after stroke, and seven biomarkers being predictive for cognitive recovery. Twelve meta-analyses were performed using effect sizes (random-effects and fixed-effects model). The most significant correlation findings obtained after pooling were with miR-21, miR-29b, miR-125b-5p, miR-126, and miR-335. We identified several miRNAs that were correlated with clinical outcomes of stroke severity and recovery after ischemic stroke, providing predictive information on motor and cognitive recovery. Based on the current state of research, we identified serum miR-9 and neutrophil miR-29b as the most promising biomarkers for in-depth follow-up studies, followed by serum miR-124 and plasma miR-125b.

D-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro.

PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions. Electron microscopy and oil-red staining were conducted to examine the lipid droplet accumulation. Masson's trichrome staining, colony forming, scratch assay and transwell experiment were conducted to evaluate the effect of PM2.5 exposure and D-limonene intervention on the occurrence and progression of LUAD. Potential intervention targets were found by RNA-Seq and verified by luciferase reporter assay. MiR-195 KO mice constructed with CRISPR/Cas9 technology were used to investigate the pivotal role of D-limonene-miR-195-SREBP1/FASN axis. Cohort analysis of lung cancer patients, human LUAD tissues staining and human intervention trial were also conducted to validate the results of cell and animal experiments. Our results showed that PM2.5 exposure induced accumulation of lipid droplets in LUAD cells which accompanied by increased malignant cellular behaviors. PM2.5 exposure led to cleaved N-SREBP1 translocation into nucleus, which activated the de novo lipogenesis pathway. Same changes were also observed in normal lung epithelial cells and normal lung tissue, and mice developed pulmonary fibrosis after long-term exposure to PM2.5. Furthermore, in a cohort of 11,712 lung cancer patients, significant lipid metabolism disorders were observed in higher PM2.5 polluted areas. In view of that, D-limonene was found to inhibit the changes in lipid metabolism through upregulating the expression of miR-195, which inhibited the expression of lipogenic genes (SREBF1/FASN/ACACA) specifically. And a small human intervention trial showed that serum miR-195 was upregulated after oral intake of D-limonene. Our findings reveal a new mechanism of pulmonary fibrosis and LUAD that is related to PM2.5 exposure-induced lipid droplet accumulation. We also demonstrate that D-limonene-miR-195-SREBP1/FASN axis is a potential preventive intervention for mediating the progression and development of LUAD induced by PM2.5 exposure. Trial registrationChinese Clinical Trial Registry, ChiCTR2000030200. Registered 25 February 2020, http://www.chictr.org.cn/showproj.aspx?proj=48013.

Evaluation of serum miR-216a and miR-375 as biomarkers in dogs with acute pancreatitis.

Serum microRNAs have emerged as biomarkers of various diseases. Overexpression of serum miR-216a and miR-375 occurs in dogs with experimentally induced acute pancreatitis (AP). To identify the possibility of using serum miR-216a and miR-375 as biomarkers for the diagnosis and evaluation of treatment response in dogs with naturally occurring AP. Twenty-one dogs with AP and 20 healthy dogs. Cross-sectional study. The relative expression of serum hsa-miR-216a-5p, cfa-miR-216a, and cfa-miR-375 were analyzed using reverse transcription and real-time PCR. A significant difference in the serum expression of cfa-miR-375 was found between dogs with AP (median [interquartile range] 3.59 [1.55-24.52]-fold) and healthy dogs (0.81 [0.54-2.21]-fold, P < .001), and no significant differences were observed in hsa-miR-216a-5p and cfa-miR-216a (P > .05). The area under the receiver operating characteristic curve of serum cfa-miR-375 for differentiating between AP dogs and healthy dogs was 0.84 (95% confidence interval [CI]: 0.71-0.96). The expressions of hsa-miR-216a-5p and cfa-miR-375 were positively correlated with the concentrations of serum C-reactive protein (rs =.46, rs =.48, respectively), but not with the serum specific canine pancreatic lipase. The expression of cfa-miR-375 was significantly less after treatment in dogs with AP (P=.02). Serum cfa-miR-375 could be a potential biomarker for the diagnosis and evaluation of treatment response of AP in dogs. In addition, miR-216a and miR-375 could be associated with inflammatory processes in dogs with AP.

Circulating serum miR-1246 and miR-1229 as diagnostic biomarkers in colorectal carcinoma.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Although colonoscopy is considered as the "Gold Standard" technique to detect CRC, its application is invasive and cost incurred. Thus, noninvasive or minimally invasive approaches are of utmost importance. The aberrant expression of some microRNAs (miRNAs, miRs) has been suggested in association with CRC pathogenesis. This study aimed to validate if circulating serum miR-1229 and miR-1246 are diagnostic biomarkers for CRC. Serum samples were isolated from 45 CRC patients and also 45 healthy controls (HC). The expression levels of circulating serum-derived miR-1229 and miR-1246 were evaluated by quantitative real-time polymerase chain reaction. Receiver operating characteristic (ROC) curves were constructed to evaluate the CRC diagnostic accuracy of selected miRNAs. Furthermore, the association of candidate miRNAs and clinicopathological characteristics were evaluated. Functional enrichment of the candidate miRNAs was applied using in silico tools. The expression of miR-1229 and miR-1246 was significantly higher in CRC patients than HC (P < 0.0001) and also was found in association with lymph node metastasis (P < 0.05). We demonstrated a significant up-regulation of serum-derived miR-1246 in advanced tumor-node-metastasis stage III of CRC patients (P < 0.05). Areas under the ROC curve of miR-1229 and miR-1246 were 0.81 and 0.84, respectively (P < 0.0001). We confirmed the capability of circulating serum miR-1229 and miR-1246 as novel diagnostic biomarkers for CRC.