Serum miR-21 Research Articles

The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population

AbstractBone tissue is constantly regenerated and repaired through a finely balanced process known as bone remodeling. Many miRNAs act as regulators of the signaling pathways involved in bone metabolic processes to maintain tissue homeostasis. This study aimed to assess the circulating levels of MIR21, MIR34a, and MIR155 in human serum and their bone expression, and the expression of bone turnover-related genes which can reflect the bone quality. This prospective study was conducted on 60 patients (30 males and 30 females) indicated for surgical interventions for neural decompression +/- fixation. Relative quantification of expression of MIR21, miR34a, and MIR155 and bone related genes was assayed using PCR. The serum levels of osteocalcin and Serum Bone Alkaline Phosphatase (sBAP) were assayed using a human ELISA kit. The main finding of the present work was the strong positive association between the circulating levels of only miR21 and MIR155 and their bone expression in the population under study and with bone markers and target genes Also, a positive association was found between both bone expression and circulating MIR21 levels with age and sBAP. These results suggest that the circulating levels of these microRNAs as early markers for the predication of bone quality.

Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma

Background and aimMicroRNAs (miRs) are now a well-known subject in various tumor genesis and are studied as early diagnostic biomarker. Many arrays of miRs were incorporated in the pathogenesis of HCV-related hepatocellular carcinomas (HCV-HCC). In this respect, we aimed to evaluate the diagnostic role of circulating miR-21, miR-122, and miR-222 in Egyptian patients with HCV-HCC.Patient and methodsBetween June 2018 and April 2019, a cross-sectional comparative study was designed to evaluate the circulating miR-21, miR-122, and miR-222 by quantitative Real-Time PCR. For analytical purposes, patients were categorized into three groups: chronic HCV group (CHC-group, n = 22), HCV-related liver cirrhosis (LC-group, n = 22), and HCV-related hepatocellular carcinoma (HCV-HCC-group, n = 54).ResultsSerum levels of miR-21 and miR-222 increased with the progressive course from CHC to LC and HCC; p < .001. Serum levels of miR-122 in HCC patients were significantly lower than non-HCC patients (CHC and LC patients, n = 44); p < .001. However, the differences in levels of serum miR-122 between CHC and LC were not statistically significant; P = 0.8.ROC curve analysis showed that the sensitivity and specificity of miR-21 were 61.1% and 95.5%, miR-222 were 71.7% and 93.2%, and miR-122 were 98.2% and 100%. The positive predictive value for miRNA-21, miRNA-122, and miRNA-222 were 13.4%, 93.3%, and 10.5% respectively. The Negative predictive value for miRNA-21, miRNA-122, and miRNA-222 were 94.3%, 97.8%, and 92.7% respectively.ConclusionMiR-21 and miR-222 could be potential markers for advanced liver damage, while miR-122 had the best diagnostic accuracy and could be a promising marker for detection of HCC.

Quantitative detection of miR-25 for early diagnosis, postoperative assessment and TNM staging of pancreatic cancer

Objectives: Pancreatic cancer is one of the most common malignant tumors of the digestive tract. Due to its strong concealment and rapid disease progress, it is characterized by high mortality and low cure rate. Current research focuses on screening high-risk populations, preventing the occurrence of pancreatic cancer and developing imaging technology and tumor markers for early diagnosis. This study aimed to investigate the absolute quantitative detection of microRNA-25 (miR-25) and reveal its quantitative changes in the treatment of pancreatic cancer. We compared serum miR-25 level between pancreatic cancer patients and other tumor patients, especially those with gastrointestinal cancer, to provide further evidence for early diagnosis, differential diagnosis and prognosis of pancreatic cancer. Methods: We collected serum samples from 51 pancreatic cancer patients (including 21 patients with preoperative and postoperative samples), 52 pancreatitis patients, 141 other tumor patients, and 50 healthy individuals from Huashan Hospital, Fudan University. The serum levels of miR-25, Carbohydrate Antigen 19–9 (CA19–9), Carbohydrate Antigen 125 (CA125) and Carcinoembryonic Antigen (CEA) in these populations were measured to analyze the value of miR-25 quantitative detection in the diagnosis, postoperative assessment and Tumor Node Metastasis (TNM) staging of pancreatic cancer. Results: Among the 51 pancreatic cancer patients, 50 cases (98.04 %) showed miR-25 levels above the threshold (3333 copies/μl), while all samples in normal group showed negative. The mean level of miR-25 in serum was 5707.45 ± 361.02 copies/μl. In other tumor groups, 21/141 (14.89 %) patients showed positive results and the mean miR-25 level was 847.09 ± 125.97 copies/μl. Comparing before and after operation in 21 paired samples, the level of miR-25 declined significantly after operation, with an average decline rate of 86.36 %. Conclusions: Serum miR-25 levels were significantly higher in pancreatic cancer patients compared to both normal and other tumor groups and decreased significantly after surgery. In addition, miR-25 showed higher sensitivity than common tumor markers (CA19–9, CA125, CEA) in early diagnosis of pancreatic cancer, and proved to be of significant value in evaluating the effect of surgical treatment.

Paper-Based DNA Biosensor for Rapid and Selective Detection of miR-21.

Cancer is the second leading cause of death globally, with 9.7 million fatalities in 2022. While routine screenings are vital for early detection, healthcare disparities persist, highlighting the need for equitable solutions. Recent advancements in cancer biomarker identification, particularly microRNAs (miRs), have improved early detection. MiR-21 is notably overexpressed in various cancers and can be a valuable diagnostic tool. Traditional detection methods, though accurate, are costly and complex, limiting their use in resource-limited settings. Paper-based electrochemical biosensors offer a promising alternative, providing cost-effective, sensitive, and rapid diagnostics suitable for point-of-care use. This study introduces an innovative electrochemical paper-based biosensor that leverages gold inkjet printing for the quantitative detection of miR-21. The biosensor, aimed at developing cost-effective point-of-care devices for low-resource settings, uses thiolated self-assembled monolayers to immobilize single-stranded DNA-21 (ssDNA-21) on electrodeposited gold nanoparticles (AuNPs) on the printed gold surface, facilitating specific miR-21 capture. The hybridization of ssDNA-21 with miR-21 increases the anionic barrier density, impeding electron transfer from the redox probe and resulting in a current suppression that correlates with miR-21 concentration. The biosensor exhibited a linear detection range from 1 fM to 1 nM miR-21 with a sensitivity of 7.69 fM µA-1 cm2 and a rapid response time (15 min). With a low detection limit of 0.35 fM miR-21 in serum, the biosensor also demonstrates excellent selectivity against interferent species. This study introduces an electrochemical paper-based biosensor that uses gold inkjet printing to precisely detect miR-21, a key biomarker overexpressed in various cancers. This innovative device highlights the potential for cost-effective, accessible cancer diagnostics in underserved areas.

Liquid biopsy for CNS lymphoma: CSF exosomes and CSF exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b are promising biomarkers for diagnosis.

Central nervous system lymphoma (CNSL) is a devastating disease with a poor prognosis. Early diagnosis, monitoring of the treatment response, and outcome prediction carry the utmost importance in the management of patients with CNSL. Surgical biopsy is the gold standard for tissue diagnosis, however, this procedure has potential complications. Therefore, there is a need for a method that provides information about diagnosis and patient monitoring to avoid surgical risks. The study aimed to investigate potential diagnostic biomarkers for patients with CNSL. Patients with secondary CNSL were included in this study. Serum and cerebrospinal fluid (CSF) samples were collected before treatment and after completion of the treatment. Cell-free DNA (cfDNA), exosomes, free and exosomal microRNA (miR)-15a, miR-21, miR-155, miR-210, and miR-19b in both serum and CSF were examined, and they were compared with the controls. Also, their levels before and after treatment were compared. Nine patients with the diagnosis of secondary CNSL were reviewed. cfDNA, miR-15a, and miR-155 in serum, and exosome in CSF were found to be significantly higher in CNSL patients compared to the controls. Exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b in CSF were found to be significantly higher in CNSL patients compared to controls, whereas their levels in serum were not significantly high. Our findings suggested that exosomes and exosomal miR-15a, miR-21, miR-155, miR-210 and miR-19b in CSF would be promising biomarkers for the diagnosis of patients with CNSL. Further studies are needed to confirm our findings.

Genetically conditioned interaction among microRNA-155, alpha-klotho, and intra-renal RAS in male rats: Link to CKD progression.

Incident chronic kidney disease (CKD) varies in populations with hypertension of similar severity. Proteinuria promotes CKD progression in part due to activation of plasminogen to plasmin in the podocytes, resulting in oxidative stress-mediated injury. Additional mechanisms include deficiency of renal alpha-klotho, that inhibits Wnt/beta-catenin, an up regulator of intra-renal renin angiotensin system (RAS) genes. Alpha-klotho deficiency therefore results in upregulation of the intra-renal RAS via Wnt/beta-catenin. In hypertensive, Dahl salt sensitive (DS) and spontaneously hypertensive rats (SHR), we investigated renal and vascular injury, miR-155, AT1R, alpha-klotho, and TNF-α. Hypertensive high salt DS (DS-HS), but not SHR developed proteinuria, plasminuria, and glomerulosclerosis. Compared to DS low salt (DS-LS), in hypertensive DS-HS alpha-klotho decreased 5-fold in serum and 2.6-fold in kidney, whereas serum mir-155 decreased 3.3-fold and AT1R increased 52% in kidney and 77% in aorta. AT1R, alpha-klotho, and miR-155 remained unchanged in prehypertensive and hypertensive SHR. TNF-α increased by 3-fold in serum and urine of DS-HS rats. These studies unveiled in salt sensitive DS-HS, but not in SHR, a genetically conditioned dysfunction of the intermolecular network integrated by alpha-klotho, RAS, miR-155, and TNF-α that is at the helm of their end-organ susceptibility while plasminuria may participate as a second hit.

Study on serum miR-182 as a marker for diagnosis and prognosis of cervical cancer.

Cervical cancer (CC) is a common female malignancy, with a global incidence rate second only to breast cancer. To propose a new idea for early treatment and auxiliary diagnosis of CC by exploring the diagnostic and prognostic implications of serum miR-182 in CC. We enrolled 70 CC patients, 35 cervical intraepithelial neoplasia (CIN) patients and 35 healthy controls (HCs), who visited The First Affiliated Hospital of Hainan Medical College Hospital between January 2015 and April 2016. miR-182 expression was quantified by real-time quantitative PCR and compared among the three groups. The correlation of serum miR-182 expression with patients' clinical features was evaluated. The receiver operating characteristic curve (ROC) and the Kaplan-Meier method were used to evaluate the early diagnostic value and prognostic value of serum miR-182. Cox regression analysis was performed to determine serum miR-182 expression and its important role in predicting CC patients' prognosis. Serum miR-182 expression was determined to be 0.345 ± 0.094, 0.369 ± 0.076, and 0.586 ± 0.157 in CC patients, CIN patients, and HCs, respectively (P< 0.001). Serum miR-182 expression had an obvious association with lymph node metastasis and pathological differentiation (P< 0.05). The area under the ROC curve (AUC) of serum miR-182 was 0.709 (95% CI: 0.622-0.795), the critical value was 0.456, the sensitivity was 81.4%, and the specificity was 52.9%. CC patients were grouped as either the low- (miR-182 < 0.3) or high-level group (miR-182 ⩾ 0.03) based on serum miR-182 levels, and a Cox regression model of OS was established. Serum miR-182 expression was identified as a factor independently influencing CC patients' OS (P= 0.028); the death risk of the high-level group was 3.246 times that of the low-level group. Serum miR-182 expression is not only a biomarker for early diagnosis of CC, but also one of the independent factors influencing the survival and prognosis of CC patients.

MicroRNA-223 alleviates inflammatory response in renal ischemia-reperfusion injury by targeting NLRP3.

We investigated the potential correlation between miR-223 and NAcHT, LRR, and PYd domain-containing protein 3 (NLRP3) in the context of renal ischemia-reperfusion injury (RIRI), which is a leading cause of acute renal failure with significant mortality rates. Additionally, miR-223 has been implicated in renal inflammation, further highlighting its relevance to this study. C57BL/6 male mice were used as RIRI models. After successful modeling, pathological examinations and serum creatinine and miR-223 levels were tested. Pro-inflammatory cytokine (IL-1β, IL-6, IL-8, NLPR3, TLR4) expression was detected in mice by western blot (kidney tissue) and enzyme-linked immunosorbent assay (serum). HK-2 cells were used for in vitro experiments. A hypoxia/reoxygenation (H/R) model was used, and miR-223 and pro-inflammatory cytokine levels were detected using PCR and western blot assays, respectively. A dual-luciferase reporter assay was conducted to confirm the binding of miR-223 to NLPR3. Next, NLRP3 was knocked down to determine whether the anti-inflammatory function of miR-223 is dependent on NLRP3. MiR-223 expression was lower in RIRI mice than in the sham operation group. The level of miR-223 negatively correlated with serum creatinine levels and the severity of tubule injury. Increased proinflammatory cytokine levels in RIRI mice were observed. In vitro, miR-223 alleviated the inflammatory response in H/R treated cells by inhibiting proinflammatory cytokines. Dual-luciferase reporter and western blot assays confirmed the binding of miR-223 to NLRP3. NLRP3 knockdown reversed the anti-inflammatory effects of miR-223 in HK-2 cells. MiR-223 plays an anti-inflammatory role in RIRI by targeting NLRP3 to repress pro-inflammatory factors.

Upregulation of Serum miR-132 and miR-152 in Vietnamese Patients with Heart Failure.

MicroRNAs (miRs) are emerging targets for the diagnosis, prognosis and treatment of heart failure (HF). Accumulated evidence showed that microRNA-132 (miR-132) and microRNA-152 (miR-152) play critical roles in the development of multiple pathological processes of the heart. Although their upregulations have been detected in the failing hearts of humans and animal models, little is known about the circulating levels of miR-132 and miR-152 in patients with HF. Our study was conducted from January 2022 to August 2022 at the Cardiology Department of the University Medical Center in Ho Chi Minh City, Vietnam. During study period, 36 participants were consecutively enrolled, including 18 HF patients and 18 patients who age and sex matched the non-HF controls. Serum samples of study participants were collected on admission and the expression levels of miR-132 and miR-152 were measured by quantitative reverse transcription polymerase chain reaction (RT-PCR). The comparative cycle threshold method (ΔCt) was applied to calculate the relative expression of miRs. The miR concentration in HF group was significantly lower than that in the control group. In contrast, the serum levels of miR-132 and miR-152 were significantly higher in HF patients. Further analyses of receiver operating characteristic (ROC) curve showed that miR-132 and miR-152 individually had moderate diagnostic potential for HF (with area under curve [AUC] values of 0.713 and 0.698, respectively). A positive correlation between these miRs was also confirmed. Serum miR-132 and miR-152 were upregulated in Vietnamese patients with HF and may serve as candidate biomarkers for diagnostic purposes.

Abstract We129: Endothelium-Targeted MiR-122 Inhibition Improves Vascular Endothelial Function In a High-Fat Diet Fed mice

Background: MicroRNA-122-5p (miR-122), a liver-specific miR, levels are increased in the blood during obesity and diabetes and is taken-up by the extra-hepatic tissues including vascular endothelium. Despite miR-122’s role in maintaining hepatic homeostasis, its uptake (from circulation) by other tissues disrupts their function and increases the risk of cardiovascular disorders. Hence, inhibiting extra-hepatic miR-122 is a viable approach to mitigate vascular disorders associated with diabetes. Hypothesis: Endothelium-targeted miR-122 inhibitor selectively targets miR-122 in endothelial cells and improves vascular endothelial function in high-fat-diet (HFD) fed pre-diabetic mice. Methods: To selectively inhibit miR-122 in the endothelial cells, we synthesized gamma-peptide nucleic acid miR-122 inhibitor (γP-122 I) tagged with vascular cell adhesion molecule 1 (VCAM1) targeted peptide (e-γP-122 I). The purity was assessed using HPLC. Pre-diabetic condition was induced by feeding mice with a HFD (for 8 weeks) and e-γP-122-I was injected to the HFD-fed mice (2 weeks after dietary intervention; 5 mg/kg/day, i.p., 6 weeks). MiR-122 expression was measured by real-time PCR. The vascular endothelial function was assessed by determining endothelium-dependent and independent relaxation of phenylephrine-induced precontracted aortic rings. Results were expressed as mean ± s.e.m. Results: The e-γP-122-I was &gt;95% pure. The HFD-fed mice show higher levels of serum and aortic miR-122 expression and impaired vascular endothelial function. e-γP-122-I treatment selectively inhibited aortic miR-122 expression while it has no effect on other organs (heart, kidney etc.) and improved vascular endothelial function and inflammation. Conclusions: e-γP-122-I selectively inhibits miR-122 in the endothelium and improves endothelial function in pre-diabetic mice.

Serum miR-192–5p is a promising biomarker for lethal radiation injury

In the event of a nuclear or radiation accident, rapid identification is required for those who exposed to potentially lethal dose irradiation. However, existing techniques are not adequate for the classification of lethal injury. Several studies have explored the potential of miRNAs as biomarkers for ionizing radiation injury, however, there are few miRNAs with specific expression for lethal radiation injury. Therefore, the aim of this study was to screen and validate the possibility of serum miRNAs as biomarkers of lethal radiation injury. We found the specific expression of mmu-miR-374c–5p / mmu-miR-194–5p on first day and mmu-miR-192–5p / mmu-miR-223–3p on third day in the mouse serum only under 10 Gy irradiation by miRNA sequencing and all significantly correlated with lymphocyte counts by Pearson’s correlation analysis. In addition, it was found that among the 4 candidate serum miRNAs, only highly-expressed mmu-miR-192–5p in mouse serum irradiated at lethal doses was returned to sham-like expression levels at 3 days post-irradiation with amifostine pretreatment and closely correlated with survival rate. We demonstrated for the first time that mmu-miR-192–5p screened from lethally irradiated mice sera can be used as a potential biomarker for lethal irradiation injury, which will be helpful to improve efficiency of medical treatment to minimize casualties after a large-scale nuclear accident.

Serum microRNAs as new biomarkers for detecting subclinical hemolysis in the nonacute phase of G6PD deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies worldwide. Patients with G6PD deficiency are usually asymptomatic throughout their life but can develop acute hemolysis after exposure to free radicals or certain medications. Several studies have shown that serum miRNAs can be used as prognostic biomarkers in various types of hemolytic anemias. However, the impact of G6PD deficiency on circulating miRNA profiles is largely unknown. The present study aimed to assess the use of serum miRNAs as biomarkers for detecting hemolysis in the nonacute phase of G6PD deficiency. Patients with severe or moderate G6PD Viangchan (871G > A) deficiency and normal G6PD patients were enrolled in the present study. The biochemical hemolysis indices were normal in the three groups, while the levels of serum miR-451a, miR-16, and miR-155 were significantly increased in patients with severe G6PD deficiency. In addition, 3D analysis of a set of three miRNAs (miR-451a, miR-16, and miR-155) was able to differentiate G6PD-deficient individuals from healthy individuals, suggesting that these three miRNAs may serve as potential biomarkers for patients in the nonhemolytic phase of G6PD deficiency. In conclusion, miRNAs can be utilized as additional biomarkers to detect hemolysis in the nonacute phase of G6PD deficiency.

Serum miRNA-1 may serve as a promising noninvasive biomarker for predicting treatment response in breast cancer patients receiving neoadjuvant chemotherapy

BackgroundMicroRNA-1 (miR-1) is a tumour suppressor that can inhibit cell proliferation and invasion in several cancer types. In addition, miR-1 was found to be associated with drug sensitivity. Circulating miRNAs have been proven to be potential biomarkers with predictive and prognostic value. However, studies of miR-1 expression in the serum of breast cancer (BC) patients are relatively scarce, especially in patients receiving neoadjuvant chemotherapy (NAC).MethodsSerum samples from 80 patients were collected before chemotherapy, and RT-PCR was performed to detect the serum expression of miR-1. The correlation between miR-1 expression in serum and clinicopathological factors, including pathological complete response (pCR), was analyzed by the chi-squared test and logistic regression. KEGG and GSEA analysis were also performed to determine the biological processes and signalling pathways involved.ResultsThe miR-1 high group included more patients who achieved a pCR than did the miR-1 low group (p < 0.001). Higher serum miR-1 levels showed a strong correlation with decreased ER (R = 0.368, p < 0.001) and PR (R = 0.238, p = 0.033) levels. The univariate model of miR-1 for predicting pCR achieved an AUC of 0.705 according to the ROC curve. According to the interaction analysis, miR-1 interacted with Ki67 to predict the NAC response. According to the Kaplan–Meier plot, a high serum miR-1 level was related to better disease-free survival (DFS) in the NAC cohort. KEGG analysis and GSEA results indicated that miR-1 may be related to the PPAR signalling pathway and glycolysis.ConclusionsIn summary, our data suggested that miR-1 could be a potential biomarker for pCR and survival outcomes in patients with BC treated with NAC.

Diagnostic value of galectin-3, fractalkine, IL-6, miR-21 and cardiac troponin I in human ischemic cardiomyopathy.

The primary objective of this study was to assess the diagnostic potential of galectin-3 (Gal-3), fractalkine (FKN), interleukin (IL)-6, microRNA(miR)-21, and cardiac troponin I (cTnI) in patients with ischemic cardiomyopathy (ICM). A total of 78 ICM patients (Case group) and 80 healthy volunteers (Control group) admitted to our hospital for treatment or physical examination from Aug. 2018 to Feb. 2020 were included in the current study. The serum concentration of Gal-3, FKN, IL-6, miR-21, and plasma expression of cTnI of both groups were determined. The severity of ICM was classified using New York Heart Association (NYHA) scale. When compared with the control group, the case group had a significantly high blood concentration of Gal-3, FKN, IL-6, miR-21, and cTnI (P < 0.001). NYHA class II patients had lower blood levels of Gal-3, FKN, IL-6, miR-21, and cTnI than that in patients of NYHA class III and IV without statistical significance (P > 0.05). However, statistical significance could be achieved when comparing the above-analyzed markers in patients classified between class III and IV. Correlation analysis also revealed that serum levels of Gal-3, FKN, IL-6, miR-21, and cTnI were positively correlated with NYHA classification (R = 0.564, 0.621, 0.792, 0.981, P < 0.05). Our study revealed that up-regulated serum Gal-3, FKN, IL-6, miR-21, and cTnI levels were closely related to the progression of ICM. This association implies that these biomarkers have diagnostic potential, offering a promising avenue for early detection and monitoring of ICM progression.

Differential expression of miR-21, miR-222, and Let-7b in serum and follicular fluid of polycystic ovary syndrome: Correlation with biochemical parameters

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. Recently, it was discovered that microRNAs (miRNAs), which circulate freely in the circulation or biofluids, have diagnostic or prognostic potential. The current study looked at the levels of expression of three miRNAs in the serum and follicular fluid (FF) of PCOS patients and healthy women. MethodWe have shortlisted the most studied miRNAs—miR-21, miR-222, and Let-7b—from the previous literature, followed by individual quantification using real-time polymerase chain reaction (PCR). ResultsThe present study results showed differences in the expression of miR-21, miR-222, and Let-7b in PCOS patients compared to controls. The area under the receiver operating characteristic (ROC) area under the curve (AUC) for miR-21, miR-222, and Let-7b was 0.70, 0.65, and 0.75 in serum and 0.55, 0.66, and 0.59 in FFs, respectively. The combined ROC of the three miRNAs showed an AUC 0.86 for serum and 0.62 for FF samples. miR-21 showed a positive correlation with body mass index (BMI), and luteinizing hormone (LH) level; miR-222 showed a positive correlation with LH, fasting blood sugar (FBS), and 2-h plasma glucose (PG); while anti-mullerian hormone (AMH), age, erythrocyte sedimentation rate (ESR) and 2-h PG were found to be negatively correlated with Let-b expression. Regression analyses showed a negative association of miR-21 with menarche, progesterone, menses, and antral follicle count (AFC), while serum miR-222 was associated with BMI and age. Let 7-b had a negative association with serum, oocytes, and the LH/FSH ratio. Bioinformatics indicates their predicted targets are potentially involved in microRNA in cancer, diabetes, the P53 signaling pathway, prolactin signaling, the Hippo signaling pathway, Ras signaling, and pathways in cancer. ConclusionThe study found that serum Let-7b, miR-222, and miR-21 were differentially expressed in PCOS patients, suggesting potential involvement in the pathogenesis or progression of PCOS.

Circulating miR-16 and miR-21 Levels in Multiple Myeloma: Prognostic Significance of Survival and Response to Lenalidomide Treatment.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in multiple myeloma (MM) pathogenesis by regulating gene expression. This study evaluated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide-dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both correlated with the depth of response and mir-16 with sustained response to LD treatment. Ratios of both miR-16 and miR-21 expression levels (prior to LD treatment/diagnosis) below two predicted a shorter time to response (p = 0.027) and a longer time to next treatment (p = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels correlated with disease variables and treatment outcomes.

MiR-21-Mediated Endothelial Senescence and Dysfunction Are Involved in Cigarette Smoke-Induced Pulmonary Hypertension through Activation of PI3K/AKT/mTOR Signaling.

Smoking is a pathogenic factor for pulmonary hypertension (PH). Our previous study showed that serum miR-21 levels are elevated in smokers. miR-21 is considered as engaged in the PH process; however, its mechanisms remain unclear. In this investigation, we found that in the lung tissue of smoking-induced PH patients, the levels of miR-21 and aging markers (p21 and p16) were upregulated, and the function of pulmonary vascular endothelial cells was also impaired. Exposure of mice to cigarette smoke (CS) for four months caused similar changes in lung tissues and increased pulmonary arterial pressure, which were attenuated by knockout of miR-21. Further, human umbilical vein endothelial cells (HUVECs) exposed to cigarette smoke extract (CSE) revealed upregulation of miR-21 levels, depression of PTEN, activation of PI3K/AKT/mTOR signaling, an increase in senescence indexes, and enhanced dysfunction. Inhibiting miR-21 overexpression reversed the PTEN-mTOR signaling pathway and prevented senescence and dysfunction of HUVECs. In sum, our data indicate that miR-21-mediated endothelial senescence and dysfunction are involved in CS-induced PH through the activation of PI3K/AKT/mTOR signaling, which suggests that selective miR-21 inhibition offers the potential to attenuate PH.

Correlation between miR-210 and serum levels of GGT, ALP and AST in patients with choledocholithiasis.

The purpose of this study was to explore the association between miR-210 and serum GGT, ALP and AST levels in patients with choledocholithiasis. The clinical data of 82 patients with biliary stones admitted to the hospital from May 2020 to May 2022 were collected and divided into observation group (n=40) and control group (n=42) according to whether asymptomatic combined. The relative expression level of miR-210 was measured by RT-PCR, serum GGT, ALP, and AST by rate method, and the correlation of miR-210 expression level with serum GGT, ALP, AST and the diagnostic value for choledochal stones was analyzed. The relative expression of serum GGT, ALP, AST and miR-210 were all higher than the control group (P <0.05); the relative expression level of miR-210 and serum GGT, ALP and AST, 0.756, 0.832, 0.326, r = P <0.05), 0.782, 0.776, 0.681, 0.568, respectively. Serum miR-210 level was upregulated in patients with choledocholithiasis, and its expression was positively correlated with serum GGT, ALP, and AST, which can be used for early auxiliary diagnosis of choledocholithiasis.

Serum miR‑29 is increased in mice with early liver fibrosis.

Non-alcoholic steatohepatitis (NASH) is a fatty liver disease that is not caused by alcohol consumption and is characterized by fatty degeneration, inflammation and hepatocellular damage. Therefore, predicting future fibrosis is critical in the early stages of NASH to prevent disease progression. The present study examined histological changes in the liver as well as microRNA (miR/miRNA) expression changes in the liver and serum of NASH mice model to identify potential biomarker candidates that could predict early fibrosis. This study used 6-week-old C57BL/6NJcl male mice and fed the control with a standard solid diet (CE-2) for breeding and propagation and NASH groups with a high-fat diet [choline-deficient high-fat and 0.1% (w/v) methionine supplemented diet], respectively. Agilent Technologies miRNA microarray was used to investigate microRNA expression in the liver and serum. Hematoxylin and eosin staining of the livers of the NASH group mice during the second week of feeding revealed fatty degeneration, balloon-like degeneration and inflammatory cell infiltration, confirming that the mice were in a state of NASH. The livers of the NASH group mice at 6 weeks of feeding showed fibrosis. Microarray analysis revealed that miRNAs were upregulated and 47 miRNAs were downregulated in the liver of the NASH group. Pathway analysis using OmicsNet predicted miR-29 to target collagen genes. Furthermore, miR-29 was downregulated in the livers of NASH-induced mice but upregulated in serum. These findings suggested that lower miR-29 expression in NASH-induced liver would increase collagen expression and fibrosis. Early liver fibrosis suggests that miR-29 leaks from the liver into the bloodstream, and elevated serum miR-29 levels may be a predictive biomarker for early liver fibrosis.

Serum bta-miRNA-375 as a potential biomarker for the early diagnosis of enzootic bovine leukosis.

To identify a biomarker for the early diagnosis of enzootic bovine leukosis (EBL) caused by bovine leukemia virus (BLV), we investigated the expression of a microRNA, bta-miR-375, in cattle serum. Using quantitative reverse-transcriptase PCR analysis, we measured bta-miR-375 levels in 27 samples from cattle with EBL (EBL cattle), 45 samples from animals infected with BLV but showing no clinical signs (NS cattle), and 30 samples from cattle uninfected with BLV (BLV negative cattle). In this study, we also compared the kinetics of bta-miR-375 with those of the conventional biomarkers of proviral load (PVL), lactate dehydrogenase (LDH), and thymidine kinase (TK) from the no-clinical-sign phase until EBL onset in three BLV-infected Japanese black (JB) cattle. Bta-miR-375 expression was higher in NS cattle than in BLV negative cattle (P < 0.05) and greater in EBL cattle than in BLV negative and NS cattle (P < 0.0001 for both comparisons). Receiver operating characteristic curves demonstrated that bta-miR-375 levels distinguished EBL cattle from NS cattle with high sensitivity and specificity. In NS cattle, bta-miR-375 expression was increased as early as at 2 months before EBL onset-earlier than the expression of PVL, TK, or LDH isoenzymes 2 and 3. These results suggest that serum miR-375 is a promising biomarker for the early diagnosis of EBL.