Expression Levels Of miR-145 Research Articles

CLINICAL SIGNIFICANCE OF SALIVARY MIR-21, -155, AND -375 IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF ORAL CAVITY.

The current prognostic markers in oral squamous cell carcinoma (OSCC) have limited accuracy sometimes leading to inappropriate treatment decisions. Identifying new markers would help clinicians tailor treatment plans based on the individual patient risk factors leading to improved survival rates and quality of life. To estimate the value of the miRNA expression indicators in saliva as prognostic and predictive markers of the effectiveness of neoadjuvant chemotherapy (NACT). The work is based on the results of the examination and treatment of 61 patients with stage II-IV OSCC. The miR-21, miR-155, and miR-375 expression levels in the saliva samples were analyzed by the real-time reverse transcription polymerase chain reaction. The salivary miR-21 and -155 expression levels in healthy volunteers were 2.49 and 2.84 times lower than in OSCС patients (p < 0.05). The positive association of miR-21 and miR-155 expression levels and the negative correlation of miR-375 expression level with T index by TNM (r = 0.68, r = 0.75, and r = -0.67, respectively) (p < 0.05) and the presence of lymph node metastasis (r = 0.78, r = 0.71, and r = ‒0.59, respectively) (p < 0.05) were found. Patients with good response to NACT had lower miR-21 and -155, and higher miR-375 levels in saliva compared to those with resistant tumors. Our study suggests that salivary miR-21, miR-155, and miR-375 may be potential biomarkers for the prognosis of cancer course and the response to NACT in OSCC patients.

Profiling mRNA and miRNA expression variations associated with cyclin-dependent kinase pathway in the low-grade luminal early breast cancer.

Luminal A and B subtypes of breast tumors have fluctuated in proliferation rates, which arise from cell cycle dysregulation in cancer. Besides, microRNAs can regulate various cell processes through integration with mRNA. miRNAs that target the cell cycle are significant because of their prediction capability of prognosis. The objective of this study is to discover the integration between miRNA-mRNA and miRNA-miRNA related to cyclin-dependent kinase. Thirty-four pairs of human primary breast cancer and tumor margin samples from luminal breast cancer patients were investigated to assess the expression levels of CCND1, E2F1, miR-124, miR-503, miR-449a, and miR-449b. Afterward, the expression levels of mRNAs and miRNAs were investigated by real-time PCR. Statistical analysis was conducted to compare the expression levels between breast cancer and corresponding normal tissues. The protein expressions of E2F1 and CCND1 were verified by western blotting. Further, the correlation between mRNAs and miRNAs was calculated. E2F1 was significantly increased in both luminal A and B patients, while CCND1 was upregulated only in luminal B. Significant differences in all miRNAs were detected in both luminal A and B biopsy specimens (p < 0.0001). The correlation analysis revealed a positive strong correlation between miR-124 and E2F1 in luminal A patient. Moreover, the correlation test confirmed the ability of miR-449a to increase the CCND1 gene in luminal B subtypes. Also, miRNA correlation exhibited the miRNA-miRNA interaction in luminal breast cancer. This study demonstrated the novel miRNA-mRNA and miRNA-miRNA interactions, providing new insights into the molecular integration in luminal A and B patients. The authors propose that this research could contribute to introducing valuable biomarkers for luminal cancerous cells.

Endometriotic lesions and their recurrence: A Study on the mediators of immunoregulatory (TGF-β/miR-20a) and stemness (NANOG/miR-145)

Endometriosis is a common estrogen-dependent disease that involves various cellular processes. Additionally, miRNAs play a crucial role in the development of the disease as an important component of the microenvironment. In this study, tissue specimens of eutopic and ectopic lesions of 20 women, whose endometriosis was later approved by the pathology laboratory, were biopsied through laparoscopy. As a control group, endometrial tissue specimens were collected from 20 women who underwent curettage for reasons unrelated to endometriosis. The expression levels of miR-20A and miR-145 and their target genes, TGF-β and NANOG, were measured in these samples as markers of stemness and immunomodulatory properties, respectively. The study also aimed to compare the expression levels of target genes and miRNAs in ectopic lesions regarding endometriosis recurrence post-surgery. The study revealed that the expression of TGF-β and NANOG genes was significantly upregulated in endometriotic tissues compared to the control group. There was also a notable increase in miR-20A and miR-145 expression in the endometriotic tissues compared to the control group. While there was no significant correlation between the expression of miR-20a and TGF-β, we observed a negative correlation between the expression level of miR-145 and NANOG. Additionally, the ROC curve analysis emphasized miR-14 as a potential biomarker for endometriosis over miR-20a. However, our findings on disease recurrence underscore the importance of miR-20a in the early detection of endometriosis recurrence.

Value of miR-31 and miR-150-3p as diagnostic and prognostic biomarkers for breast cancer.

The most prevalent malignancy among women is breast cancer (BC). MicroRNAs (miRNAs) play a role in the initiation and progression of BC by influencing breast cancer stem cells (BCSCs) but the diagnostic and prognostic roles of those miRNAs on BC patients are still unknown. It was aimed to investigate expression profiles, diagnostic and prognostic potentials of BCSC-related miRNAs in different subtypes (Luminal A and B, HER2 + and TNBC) of BC patients. Expression analysis of 15 BCSC-related miRNAs was performed in 50 breast tumor tissues and 20 adjacent non-tumor tissues obtained from BC patients using the qRT-PCR method. The expression levels of miR-31 and miR-150-3p were significantly upregulated in the tumor tissues compared to the adjacent non-tumor tissues (p < 0.05). miR-31 expression upregulated in the Luminal A and Luminal B group compared to non-tumor tissue (p < 0.05). miR-31 expression was determined to be significantly higher in the Luminal group (Luminal A and B) compared to the aggressive group (HER2 + and TNBC) (p < 0.05). According to the ROC analysis, the area under the curve (AUC) of miR-31 and miR-150-3p were 0.66 with a sensitivity of 68% and a specificity of 70%. A significant inverse correlation was observed between miR-31 expression with metastatic carcinoma status, in situ component, and Ki67 value in tumors, and high miR-150-3p expression was correlated with p63 expression (p < 0.05). miR-31 and miR-150-3p have the potential to serve as biomarkers for guiding diagnosis, evaluating prognosis, and metastatic process in patients with BC.

Dysregulated miR-124 mediates impaired social memory behavior caused by paternal early social isolation.

Early social isolation (SI) leads to various abnormalities in emotion and behavior during adulthood. However, the negative impact of SI on offspring remains unclear. This study has discovered that paternal early SI causes social memory deficits and anxiety-like behavior in F1 young adult mice, with alterations of myelin and synapses in the medial prefrontal cortex (mPFC). The 2-week SI in the F1 progeny exacerbates social memory impairment and hypomyelination in the mPFC. Furthermore, the down-regulation of miR-124, a key inhibitor of myelinogenesis, or over-expression of its target gene Nr4a1 in the mPFC of the F1 mice improves social interaction ability and enhances oligodendrocyte maturation and myelin formation. Mechanistically, elevated levels of miR-124 in the sperm of paternal SI mice are transmitted epigenetically to offspring, altering the expression levels of miR-124/Nr4a1/glucocorticoid receptors in mPFC oligodendrocytes. This, in turn, impedes the establishment of myelinogenesis-dependent social behavior. This study unveils a novel mechanism through which miR-124 mediates the intergenerational effects of early isolation stress, ultimately impairing the establishment of social behavior and neurodevelopment.

MicroRNA-124-3p targets Sp1 transcription factor to regulate glioma progression in rats

Gliomas are the most prevalent malignancies of the central nervous system (CNS). Downregulation of microRNA‑124 (miR‑124) has been identified in glioma; however, its biological functions in glioma are not yet fully understood. Specificity protein 1 (SP1) is a type of transcription factor that is involved in cancer progression. In this study, we examined the targeting of Sp1 mRNA by miR-124-3p in a rat glioma model. After confirming and selecting the binding of Sp1 to miR-124 with the help of bioinformatics methods, adult male Wistar rats were used to induce glioma by microinjection of 1 × 106 C6 cells into the striatum area of brain. The rats were divided into 3 groups; intact, sham and glioma groups. The presence of glioma was confirmed 21 days after implantation through histological analysis. The expression levels of miR-124 and SP1 genes in the experimental groups were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Our data showed that the expression of miR-124 was significantly downregulated in glioma group compared to the sham and intact group, while the expression of SP1 was significantly upregulated. We found that the expression levels of miR-124 and Sp1 were decreased and increased in C6 cell line compared to the normal brain tissue cell line, respectively. The results indicated that Sp1 was identified as a direct target of miR‑124 through luciferase reporter assays. In summary, this study demonstrated for the first time that miR-124 expression is downregulated and Sp1 expression is upregulated in an animal model of glioma, which, in turn, may be involved in the development of glioma brain cancer.

IL-32 regulates trophoblast invasion through miR-205-NFκB-MMP2/9 axis contributing to the pregnancy-induced hypertension†.

Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signaling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.

Evaluation of the Plasma Expression Levels of miR-21 and miR-145 as Potential Non-Invasive Biomarkers for Early Detection of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. Early detection would be greatly enhanced if accurate and cost-effective diagnostic biomarkers for CRC were accessible. The development of blood tests would evidently lower the screening cost of CRC detection. The aim of the present study was to examine the prospective of plasma miRNAs as non-invasive biomarkers for CRC screening. The expressions of miR-21 and miR-145 in the plasma of colorectal adenocarcinomas and normal healthy controls were quantified by using TaqMan miRNA assays. MiRNA expression levels were also correlated with commonly used clinicopathological features of CRC. Out of 30 CRC patients, 19 were male and 11 were female. The Mean age of patients was 51.3 ±14.6 years. A statistically significant increase in expression of miR-21 was observed in CRC patients' as compared to healthy controls (p<0.001). A significant association between miR-21 expression and age group (p=0.002) was noticed. Also, a statistically significant difference (p=0.015) between miR-21 expression and tumor location in the proximal and distal sites of the colon was observed in CRC patients. Further, a statistically significant downregulation of miR-145 expression was observed in the plasma of CRC patients as compared to healthy controls (p<0.05). This is the first study to report a significant association between miR-21 expression, age group, and tumor location in CRC patients. The present study thus emphasises that the appraisal of miR-21 and miR-145 plasma levels may serve as a promising non-invasive screening tool for the early detection of colorectal cancer.

A Study on the Role of miR-126 in the Repair Process after Spinal Cord Injury

Background: Spinal Cord Injury (SCI) results in motor, sensory, and autonomic dysfunctions and causes social and economic problems. Surgery, medication, and stem cell transplantation are therapeutic strategies for SCI. The use of endogenous neural stem cells seems preferable due to their lower immune responses. miR-126 serves as a promising microRNA for reducing inflammation after SCI. It can promote angiogenesis and proliferation of neural stem cells Objectives: This study aimed to observe changes in miR-126 expression after SCI in an animal mice model. Methods: A total of 42 healthy adult FVB mice were divided equally into 7 groups (6 SCI model versus 1 control). At different periods following SCI establishment in the model groups, Basso Mouse Scale score (BMS), histopathological changes, and expression levels of miR-126 were evaluated in the model groups compared to the control one. Results:: The BMS score increased to a certain extent as the time after spinal cord injury progressed. HE and Nissl staining showed that the acute period (1-7 days) after spinal cord injury was characterized by neuronal loss, whereas the chronic phase (21st day) was characterized by scar and cavity formation. Compared with the control group, the model group exhibited decreased expression of miR-126 during the acute phase (days 1-7 post-SCI). However, its expression increased by 21th day after SCI. Conclusion: Overexpressed miR-126 can contribute to reduced SCI-related damages, which may result in the promotion of the growth and proliferation of neural stem cells as well as the repair of motor function.

Linoleic Acid Modulates the Expression of Metastatic and Angiogenic Markers MMP-2 and Talin-2 in Gastric Cancer Cell Line MKN-45.

Linoleic acid (LA) has modulatory effects on gastric cancer cell lines. This study aimed to investigate the effects of linoleic acid on the expression of metastatic and angiogenic molecular markers in gastric cancer cell line MKN-45. In this study performed in Tabriz, Iran in 2021, MKN-45 cells were treated with LA in the presence or absence of docetaxel. Total RNA was extracted, and cDNA synthesized from the cells before and after treatment. The expression levels of Talin-2 and MMP-2 genes and mir-20, mir-30, mir-126, and mir-194, were determined by quantitative real-time PCR. LA treatment reduced the expression levels of mir-126, mir-194, mir-30, and MMP-2, while increased the expression levels of Talin-2 mRNA. Docetaxel treatment could decrease the expression levels of mir-20, Talin-2, and MMP-2 mRNA levels while increasing the expression levels of mir-126, mir-194, and mir-30. Additionally, the combined treatment of MKN-45 cells with LA and docetaxel could reduce the expression levels of mir-20 and mir-126 and increased the expression levels of mir-194, mir-30, Talin-2, and MMP-2 mRNAs. Modulation of the expression levels of gastric cancer involved microRNAs, Talin-2, and MMP-2 may be a mechanism through which LA may exert its biological effects on GC cell line MKN-45. LA may have an antimetastatic effect by reducing the MMP-2 expression and pro-angiogenic effect through increasing Talin-2 expression levels.

The Role of Epstein-Barr Virus (EBV) Infected Gastric Cancer in Increasing microRNA124 (miR-124) Promoter Methylation and Enhancer of Zeste Homolog 2 (EZH2) Gene Expression.

The tumor suppressor microRNAs, miR-21, miR-124, and miR-494, participate in the controlling several cellular processes. To assess target miRNAs promoter methylation levels, we investigated 304 pairs of gastric cancer (GC) tissues and non-tumor tissues. We used a commercial real-time polymerase chain reaction (RT-PCR) for Epstein-Barr virus (EBV) and Helicobacter pylori kit to detect EBV and H. pylori DNA in GC tissues. After finding hypermethylation in the promoter of the miR-124 gene, we evaluated its expression level using quantitative PCR (qPCR). Bioinformatics analysis confirmed miR-124 as a target of enhancer of Zeste homolog 2 (EZH2). Additionally, qPCR confirmed the association between EZH2 and miR-124. EBV and H. pylori DNA were detected in 9.5% and 15.1% of GC patients, respectively. Our findings also revealed significant differences in the miR-124 methylation levels among EBV-infected GC patients, H. pylori infected GC patients, GC patients without EBV and H. pylori infection, and non-tumor tissue. Bioinformatics and qPCR assays suggested an inverse relationship between the expression levels of EZH2 and miR-124 in EBV-infected GC patients. Our data revealed hypermethylation of the miR-124 promoter and significant reduction in its expression in EBV-infected GC tissues. It is possible that miR-124 may target EZH2 by binding to the 3'-UTR of the EZH2 gene, thus potentially contributing to the development of EBV-infected GC.

Correlation analysis of serum miR-145 and miR-210 with carotid artery stenosis and their predictive value for cerebral ischemic events

Objective To analyze the significance of serum miR-145 and miR-210 expression levels in the diagnosis of carotid artery stenosis. Methods During the same period, 55 healthy individuals who received physical examination in the same hospital were recruited as controls and assigned to a non-stenosis group. Among the included patients, there were 45 cases of mild stenosis, 14 cases of moderate stenosis, and 6 cases of severe stenosis after carotid color Doppler ultrasonography. The expression levels of miR-145 and miR-210 in serum were measured using real-time fluorescence quantitative polymerase chain reaction (qPCR) technology. Results The expression levels of serum miR-145 and miR-210 in carotid artery stenosis group were significantly lower than those in non-stenosis group (p < 0.001). Multivariate Logistic regression analysis showed that smoking history, diabetes, hypertension and total cholesterol were positively correlated with the occurrence of carotid artery stenosis (p < 0.05). The expression levels of miR-145 and miR-210 were significantly negatively correlated with carotid artery stenosis (p < 0.001). In addition, patients with carotid artery stenosis and low expression levels of miR-145 and miR-210 had a greater risk of cerebral ischemia (p < 0.05). Cox regression analysis showed that the low expression of miR-145 and miR-210 were independent predictors of cerebral ischemic events. ROC analysis confirmed that miR-145 and miR-210 had good diagnostic efficacy in cerebral ischemia (p < 0.001). Conclusion The decreased expression of miR-145 and miR-210 in serum is closely related to the diagnostic significance of carotid artery stenosis, and may be used to predict the occurrence of cerebral ischemic events.

Effects of miR-214 on adenosine A2A receptor and carboxymethyl chitosan nanoparticles on the function of keloid fibroblasts and their mechanisms

This work prepared and investigated the impact of carboxymethyl chitosan nanoparticles (MC-NPs) on the proliferative capability of keloid fibroblasts (KFBs) while analyzing the mechanistic roles of miR-214 and adenosine A2A receptor (A2AR) in fibroblasts within hypertrophic scars. MC-NPs were synthesized through ion cross-linking, were characterized using transmission electron microscopy (TEM) and laser particle size scattering. The influence of MC-NPs on the proliferation capacity of KFBs was assessed using the MTT method. Changes in the expression levels of miR-214 and A2AR in KFBs, normal skin fibroblasts (NFBs), hypertrophic scar tissue, and normal skin tissue were analyzed. KFBs were categorized into anti-miR-214, anti-miR-NC, miR-214 mimics, miR-NC, si-A2AR, si-con, anti-miR-214+ si-con, and anti-miR-214+ si-A2AR groups. Bioinformatics target prediction was conducted to explore the interaction between miR-214 and A2AR. Real-time quantitative PCR and immunoblotting (WB) were employed to detect the expression levels of miR-214, A2AR, apoptotic protein Bax, and TGF-β in different cells. Cell counting kit-8 (CCK8) and flow cytometry were employed to assess cell proliferation activity and apoptosis. The results indicated that MC-NPs exhibited spherical particles with an average diameter of 236.47 ± 4.98 nm. The cell OD value in the MC-NPs group was lower than that in KFBs (P < 0.05). The mRNA levels of miR-214 in KFBs and hypertrophic scar tissue were lower than those in NFBs and normal tissue (P < 0.001), while the mRNA and protein levels of A2AR were significantly elevated (P < 0.05). Compared to the control group and anti-miR-NC, the anti-miR-214 group showed significantly increased cell OD values and Bcl-2 protein expression (P < 0.001), decreased levels of apoptotic gene Bax protein, TGF-β gene mRNA, and protein expression (P < 0.001). Continuous complementary binding sites were identified between miR-214 and A2AR. Compared to the control group, the si-A2AR group exhibited a significant decrease in A2AR gene mRNA and protein expression levels (P < 0.001), reduced cell viability (P < 0.001), increased apoptosis rate (P < 0.001), and a significant elevation in TGF-β protein expression (P < 0.001). miR-214 targetedly regulated the expression of A2AR, inducing changes in TGF-β content, promoting the proliferation of keloid fibroblasts, and inhibiting cell apoptosis.

Association of ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 with esophageal cancer.

In India, esophageal cancer (EC) is among the major cause of cancer-related deaths in both sexes. In recent past, autophagy has emerged as one of the crucial process associated with cancer. In the development of EC, the role of autophagy and the precise molecular mechanism involved has yet to be fully understood. Recently, a small number of studies have proposed how variations in autophagy genes affect the growth and development of EC. Micro-RNA's are also known to play a critical role in the development of EC. Here, we examined the relationship between the risk of EC and two single-nucleotide polymorphisms (SNPs) in the key autophagy genes, ATG10 rs1864183 and ATG16L1 rs2241880. We also analyzed the association of miR-107 and miR-126 with EC as these miRNA's are associated with autophagy. A total of 230 EC patients and 230 healthy controls from North-west Indian population were enrolled. ATG10 rs1864183 and ATG16L1 rs2241880 polymorphism were analyzed using TaqMan genotyping assay. Expression levels of miR-107 and miR-126 were analyzed through quantitative PCR using SYBR green chemistry. We found significant association of CT + CC genotype (OR 0.64, p = 0.022) in recessive model for ATG10 rs1864183 polymorphism with decreased EC risk. For ATG16L1 rs2241880 polymorphism significant association for AG genotype (OR 1.48, p = 0.05) and G allele (OR 1.43, p = 0.025) was observed for increased EC risk. Expression levels of miR-126 were also found to be significantly up regulated (p = 0.008). Our results suggest that ATG10 rs1864183, ATG16L1 rs2241880 and miR-126 may be associated with esophageal carcinogenesis and warrant further investigation.

Clinical importance of serum miRNA levels in breast cancer patients

There is limited data on the relationship of miRNAs with parameters that may affect surgical management or reflect tumour prognosis. It was aimed to evaluate serum miRNA levels in breast carcinoma cases and reveal the relationship between these levels and prognosis-related factors such as the histological type of the tumour, estrogen receptor, progesterone receptor, Ki-67 index, HER-2neu, E-cadherin, tumour size, CK5/6, CA15.3 levels, number of tumour foci, number of metastatic lymph nodes, and status of receiving neoadjuvant therapy. Thirty-five patients with a histopathologically confirmed breast carcinoma diagnosis in the case group and 35 healthy individuals in the control group were examined. miR-206, miR-17-5p, miR-125a, miR-125b, miR-200a, Let-7a, miR-34a, miR-31, miR-21, miR-155, miR-10b, miR-373, miR-520c, miR-210, miR-145, miR-139-5p, miR-195, miR-99a, miR-497 and miR-205 expression levels in the serum of participants were determined using the Polymerase Chain Reaction method. While serum miR-125b and Let-7a expression levels were significantly higher in breast cancer patients, miR-17-5p, miR-125a, miR-200a, miR-34a, miR-21, miR-99a and miR-497 levels were significantly lower in them. The Let-7a expression level had a statistically significant relationship with breast cancer histological type and HER-2neu parameters, miR-17-5p, miR-125b, Let-7a, miR-34a, miR-21 and miR-99a levels with E-cadherin, miR-34a, miR-99a and miR-497 with CA15.3, miR-125b, miR-200a and miR-34a with the number of metastatic lymph nodes, miR-125a with the number of tumour foci and miR-200a with the status of having the neoadjuvant therapy. Serum miR-17-5p, miR-125a, miR-125b, miR-200a, Let-7a, miR-34a, miR-21, miR-99a and miR-497 expression levels were determined to have predictive and prognostic importance in breast cancer.

High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: the HUNT study

AbstractMicroRNA-145 (miR-145) has been reported to downregulate the expression of tissue factor and factor XI in vitro and decrease venous thrombus formation in animal models. However, the association between miR-145 and risk of future venous thromboembolism (VTE) in the general population remains unknown. We investigated the association between plasma levels of miR-145 and risk of future VTE in a case-cohort study. Incident VTE cases (n = 510) and a subcohort (n = 1890) were derived from the third survey of the Trøndelag Health Study (HUNT3), a population-based cohort. The expression levels of miR-145 were measured in plasma samples obtained at baseline. The study population was divided into quartiles based on miR-145 levels in participants in the subcohort, and weighted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma levels of miR-145 were inversely associated with VTE risk. Participants with miR-145 levels in the highest quartile had a 49% lower risk of VTE (HR, 0.51; 95% CI, 0.38-0.68) than those with miR-145 in the lowest quartile in age- and sex-adjusted analysis, and the inverse association was most pronounced for unprovoked VTE (HR, 0.39; 95% CI, 0.25-0.61). Risk estimates remained virtually the same after further adjustment for body mass index, and cancer and arterial cardiovascular disease at baseline. In conclusion, elevated expression levels of miR-145 in plasma were associated with decreased risk of future incident VTE. The protective role of miR-145 against VTE is consistent with previous experimental data and suggests that miR-145 has the potential to be a target for VTE prevention.

Prognostic value of plasma microRNAs for non-small cell lung cancer based on data mining models

BackgroundAs biomarkers, microRNAs (miRNAs) are closely associated with the occurrence, progression, and prognosis of non-small cell lung cancer (NSCLC). However, the prognostic predictive value of miRNAs in NSCLC has rarely been explored. In this study, the value in prognosis prediction of NSCLC was mined based on data mining models using clinical data and plasma miRNAs biomarkers.MethodsA total of 69 patients were included in this prospective cohort study. After informed consent, they filled out questionnaires and had their peripheral blood collected. The expressions of plasma miRNAs were examined by quantitative polymerase chain reaction (qPCR). The Whitney U test was used to analyze non-normally distributed data. Kaplan-Meier was used to plot the survival curve, the log-rank test was used to compare with the overall survival curve, and the Cox proportional hazards model was used to screen the factors related to the prognosis of lung cancer. Data mining techniques were utilized to predict the prognostic status of patients.ResultsWe identified that smoking (HR = 2.406, 95% CI = 1.256–4.611), clinical stage III + IV (HR = 5.389, 95% CI = 2.290-12.684), the high expression group of miR-20a (HR = 4.420, 95% CI = 1.760–11.100), the high expression group of miR-197 (HR = 3.828, 95% CI = 1.778–8.245), the low expression group of miR-145 ( HR = 0.286, 95% CI = 0.116–0.709), and the low expression group of miR-30a (HR = 0.307, 95% CI = 0.133–0.706) was associated with worse prognosis. Among the five data mining models, the decision trees (DT) C5.0 model performs the best, with accuracy and Area Under Curve (AUC) of 93.75% and 0.929 (0.685, 0.997), respectively.ConclusionThe results showed that the high expression level of miR-20a and miR-197, the low expression level of miR-145 and miR-30a were strongly associated with poorer prognosis in NSCLC patients, and the DT C5.0 model may serve as a novel, accurate, method for predicting prognosis of NSCLC.

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&lt;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&lt;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&lt;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.

Dysregulated miRNA-375, IL-17, TGF-β, and Microminerals Are Associated with Calpain-10 SNP 19 in Diabetic Patients: Correlation with Diabetic Nephropathy Stages.

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-β and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-β, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-β, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-β, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-β, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-β, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

MIR-145's Regulatory Role in Breast Cancer Progression

Delayed diagnosis of breast cancer results in lower treatment success rates and lower survival rates. Every year millions of women are diagnosed with breast cancer and many of them die from this disease. However, the discovery of biomarkers that enable early diagnosis should increase the success of treatment processes and extend survival times. In recent years, studies have been carried out to use microRNAs as biomarkers in the early detection of breast cancer. Research shows that microRNAs can serve as potential biomarkers for the diagnosis and prognosis of breast cancer. In addition to ongoing research on the possible use of microRNAs as biomarkers for early breast cancer diagnosis, our study also analyzed the possible use of miR-145 as a biomarker in breast cancer. In our study, RNA samples were isolated from blood serum samples of 200 breast cancer patients and 100 people in the healthy control group, and the specific expression levels of miR-145 were determined using RT-qPCR technique. As a result of these analyses, it was found that miR-145 had lower expression levels in breast cancer patients than in healthy controls. After further investigation of the biomarker potential of miR-145 in a larger group of breast cancer patients, it will be used as a target biomarker for early breast cancer diagnosis.