mir-1

Type 2 diabetes mellitus (T2DM), the most prevalent metabolic disorder worldwide, has genetic, epigenetic, and environmental contributors. Among them, circulating microRNAs (miRNAs/miRs) have attracted considerable attention. This study aimed to investigate the regulatory role of miR-103 in T2DM development.

The miR-103 expression was evaluated in 33 participants with T2DM compared with 38 healthy controls using quantitative real-time polymerase chain reaction (q-RT PCR). Fasting blood glucose (FBS), fasting insulin (Fin), hemoglobin A1c (HbA1c), triglycerides (TG), and cholesterol (Chol) were also determined in serum. Basal insulin resistance and sensitivity were determined using the homeostasis model assessment insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI), respectively.

There was a significant decrease in miR-103 levels in patients with T2DM (p<0.002). Serum miR-103 expression levels showed a strong correlation with age, FBS, HbA1c, TG, Chol levels, and HOMA-IR and QUICKI indices.

The downregulation of miR-103 in T2DM patients suggests the diagnostic potential of miR-103 evaluation in conjunction with other diagnostic approaches.

Myocardial ischemia/reperfusion injury (MIRI) is the primary pathological injury following ischemic cardiomyocyte therapy, but there are few effective treatments available for MIRI. Apigenin (API) is an active ingredient of herbal medicine. Our study aims to verify whether API regulates autophagy and apoptosis against MIRI via miR-448/Sirtuin-1 (SIRT1) axis.

MTT, SOD, and LDH assays were used to measure cell viability, oxidative stress injury, and cell damage, respectively. RT-qPCR, western blot, and ELISA were used to measure RNA and protein expression levels.

Compared with the control group, cell viability and SOD levels in the cells of the OGD/R group were significantly decreased, LDH release in the cells was significantly increased, the level of miR-448 in the cells was significantly increased, the levels of SIRT1 mRNA and protein in the cells were significantly increased, the expression of LCII/I and Bcl-2 proteins in the cells were significantly down-regulated, and the expression of p62, Bax proteins in the cells and caspase-3 protein in the cell supernatant were significantly up-regulated. Compared with the OGD/R group, the above indicators were significantly reversed in the OGD/R+API group and the OGD/R+miR-448 inhibitor group. Compared to the OGD/R+miR-448 inhibitor group, the above indicators were significantly reversed in the OGD/R+miR-448 inhibitor+EX527 (SIRT1 inhibitor) group. Compared to the OGD/R+API group, the above indicators were significantly reversed in the OGD/R+API+miR-448 mimic group, OGD/R+API+EX527 group, and OGD/R+API+CA-5f (autophagy inhibitor) group.

API regulates autophagy and apoptosis via the miR-448/SIRT1 axis against MIRI.

Aberrant methylation and expression of various noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), confer a great potential as tumor markers. This study aimed to investigate miR-30b DNA methylation and metastasis associated lung adenocarcinoma transcript 1 (MALAT-1) expression patterns as potential diagnostic biomarkers for non-small cell lung cancer (NSCLC). In this cross-sectional study, miR-30b DNA methylation and MALAT-1 expression patterns were first explored using microarray data retrieved from the NSCLC dataset in the Cancer Genome Atlas (TCGA)-LUNG. Then, the obtained results were further validated in internal samples. Subsequently, genomic DNA was extracted and modified by sodium bisulfite to determine DNA methylation using q-MSP. Total RNA was extracted and transcribed to cDNA to measure transcription level by quantitative real-time polymerase chain reaction. GraphPad 6 Prism v.8 was used to perform the statistical analyses. Comparisons between groups in internal samples were conducted by paired student's t-test, while Mann-Whitney U test was used to analyze TCGA-LUNG data (P < 0.05). Our results indicated miR-30b hypermethylation, miR-30b downregulation and lncRNA MALAT-1 overexpression in NSCLC tumor samples compared with marginal normal samples. These changes were significantly associated with the stage of malignancy like lymph node metastasis. Also, using receiver operating characteristic curve analysis, MALAT-1 expression, and miR-30b methylation and expression patterns were found as possible diagnostic biomarkers for NSCLC (area under the curve was 0.70, 0.67, and 0.74, respectively). We found involvement of miR-30b hypermethylation and downregulation as well as lncRNA MALAT-1 overexpression with tumor outcomes of NSCLC patients.

Circular RNAs are involved in the tumorigenesis of various tumors, including Non-small cell lung cancer (NSCLC).

To investigate the expression of circ_0001006 in patients with NSCLC and its role in tumorigenesis and immune escape.

A total of 115 patients with NSCLC were enrolled in the study. The expression of circ_0001006 and PD-L1 mRNA were detected using RT-qPCR. Cell proliferation activity, cell migration and invasion abilities were measured using the CCK-8 assay and Transwell chambers assay. Coculture of NSCLC cells with CD8 cytotoxic T cells was conducted to measure the levels of INF-γ, TNF-α, IL-2, and lactate dehydrogenase release in culture supernatants. Bioinformatic analysis was used to predict the target relevance among circ_0001006, miR-320a, and PD-L1.

The circ_0001006 and PD-L1 mRNA levels were elevated in NSCLC tissues and cells. Patients with high levels of circ_0001006 had a shorter overall survival rate. Inhibiting circ_0001006 reduced the proliferation, migration, and invasion of NSCLC cells, while increasing PD-L1 partially counteracting the inhibitory effects of si-circ_0001006. The co-culture system of NSCLC and CD8+ T cell was found to reduce the viability of activated CD8+ T cell when circ_0001006 is present. Knocking down circ_0001006 in co-culture cells led to an increase in the expression of INF-γ, TNF-α, and IL-2. The ability of si-circ_0001006 to enhance the activation of CD8+ T cells was diminished when PD-L1 was overexpressed.

circ_0001006 may serve as a potential prognostic predictor and therapeutic target for NSCLC. Additionally, it offers insight into a novel regulatory mechanism of circ_0001006.

Hepatocellular carcinoma (HCC) is one of the lethal malignancies with a poor prognosis due to metastatic complications. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have an important role in metastasis. MicroRNA-21 (miR-21) is significantly overexpressed in nearly all types of human cancers, including HCC. Targeting miR-21 pharmacologically could be a promising therapeutic approach for HCC. 3,4-dihydroxyphenylethanol (DHPE), a phenolic phytochemical compound found in olive, has potent antioxidant and anticancer properties. This study aimed to investigate the effect of DHPE on the expression of miR-21 with genes associated with metastasis (MMP-2, MMP-9, TIMP-1, and TIMP-2) and their correlation with miR-21 in HepG2 cells.

This experimental study had four groups, including a control, and three groups of treatment with different concentrations of DHPE (50, 100, and 150 µM) for 24 hours. The expression levels of genes were determined by RT-qPCR.

The results showed that the treatment of cells with DHPE significantly reduced the expression of miR-21, MMP-2, MMP-9, and TIMP-1 but increased TIMP-2 compared to the control group; additionally, there was a negative correlation between miR-21 and TIMP-2 but a positive correlation between miR-21 with MMP-2, MMP-9, and TIMP-1.

The results showed that DHPE, likely by reducing the expression of miR-21, can increase TIMP-2 and reduce MMP-2, MMP-9, and TIMP-1 gene expression and may play a role in inhibiting cell migration in HepG2 cells.

Breast cancer, characterized by genetic diversity and molecular subtypes, presents significant treatment challenges, especially in human epidermal growth factor receptor type 2 (HER2)-positive cases, which are associated with poor prognosis. Metformin, widely known for its antidiabetic effects, has emerged as a promising candidate for cancer therapy. This study investigates the effect of metformin on miR-125a promoter methylation and its subsequent impact on the HER2 signaling pathway in HER2-positive breast cancer cells (SK-BR3). SK-BR3 cells were cultured and treated with various concentrations of metformin to assess its effects on cell viability, DNA methylation, HER2, and DNA Methyltransferase 1 (DNMT1) expression. Molecular analyses focus on the miR-125a signaling pathway modulation, DNA methylation, mRNA expression of DNMT1, and protein level of HER2. Research showed a dose-dependent reduction in cell viability, with IC50 values from 65 mM at 48 hours to 35 mM at 72 hours. Metformin treatment led to demethylation of the miR-125a promoter, which increased miR-125a expression and subsequently reduced HER2 levels. This suggests that metformin exerts its anticancer effects partly by regulation of the miR-125a-HER2 axis. Additionally, metformin inhibited vimentin expression, indicating its potential to interfere with epithelial-mesenchymal transition (EMT) processes. Metformin may serve as a targeted therapeutic agent in HER2-positive breast cancer by modulating the miR-125a-HER2 axis and influencing on the epigenetic and EMT regulation. Further research is warranted to elucidate the therapeutic potential of metformin through these mechanisms.

In recent years, the application of herbal compounds in cancer treatment has shown significant progress. Curcumin (CUR), a natural polyphenol, demonstrates potent anti-cancer effects against various cancers, including breast cancer (BC). Curcumin targets a range of molecular pathways, contributing to the inhibition of cancer cell proliferation, metastasis, and angiogenesis, and promoting apoptosis.

This study aimed to assess the effect of CUR on BC cells, focusing on alterations in the expression levels of Mir-15a and Bcl-2 through the apoptotic pathway.

The cytotoxicity of CUR was evaluated using an MTT assay. Changes in the expression of Mir-15a and Bcl-2 genes were analyzed by real-time PCR, and cell apoptosis was measured using flow cytometry. Data analysis was conducted using SPSS.

The MTT assay results indicated that cell viability decreased as CUR concentration increased (5 – 25 µM). Real-time PCR results showed a significant decrease in the expression of Mir-15a and Bcl-2 (P < 0.05). Flow cytometry findings demonstrated that CUR treatment at the IC50 concentration for 48 hours induced apoptosis in 75.9% of MCF-7 cells.

Our study provides a crucial foundation indicating that CUR induces apoptosis in MCF-7 cells by modulating the expression of Mir-15a.

Cervical cancer is the fourth most common cancer among women. In recent years, significant progress has been made in its treatment. Quercetin, a polyphenolic compound found in flavonoid-containing plants, is of interest due to its potential therapeutic effects. miR-21 plays a crucial role in cervical tumor metastasis by activating pathways related to invasion and migration, while miR-34a-5p is essential in regulating epithelial-to-mesenchymal transition and preventing increased cell proliferation and migration. The findings of this study could provide insight into the role of quercetin in cancer cells.

This study aims to investigate the effect of quercetin on the expression levels of miR-21 and miR-34a-5p in HeLa and Ca Ski cervical cancer cell lines.

In this study, HeLa and Ca Ski cells were treated with quercetin. Cell viability and apoptosis were evaluated using the MTT assay and flow cytometry over a 48-hour period. Additionally, the effects of quercetin on the expression levels of miR-21 and miR-34a-5p were analyzed using qRT-PCR.

The study demonstrated that quercetin inhibited the viability of HeLa and Ca Ski cells and induced apoptosis in these cells. Quercetin suppressed cell viability with an IC 50 of 102.9 μM for HeLa and 304.1 μM for Ca Ski cells after 48 hours. Quercetin down-regulated miR-21 in HeLa and Ca Ski cell lines by 2.5 ± 0.1 (P = 0.045) and 2.0 ± 0.2 (P = 0.016) fold, respectively. Additionally, miR-34a-5p increased by 3.3 ± 0.7 (P = 0.010) and 2.4 ± 0.8 (P = 0.047) fold after exposure to quercetin in HeLa and Ca Ski cell lines, respectively.

Our study showed that quercetin has an anti-cervical cancer effect and can be used alongside standard therapies as a promising agent with fewer side effects in cervical cancer treatment.

Cancer is a disease caused by manifestation and abnormal gene expression. Many of the genes that inhibit cancer by the microRNAs. The aim of this study was to investigate the Expression of miR155 gene and CEA and VEGF proteins as Diagnostic Markers in Early Stages of Non-Small Cell Lung Cancer (NSCLC).

Fifty pairs of non-small lung cancer specimens of patients from healthy and tumors specimens were collected based on physical examination and diagnosis of an expert, that, in Masih Daneshvari Hospital. 50 healthy volunteers as a control group were volunteered by the physician after examination and filled out the consent form in this study. From all subjects, 6 ml of peripheral blood were taken and examined by Real-Time PCR (RT-PCR) and ELISA.

The expression level of miR-155 in patients was significantly increased compared to the control group (p<0.001). VEGF protein was positive in 34 of the 50 patients and in healthy subjects, 3 persons were positive. The statistical comparison of the amount of positive biomarker was performed in two groups and it was shown that there is a statistically significant difference between these two groups (P<0.001). CEA protein was positive in 38 of the 50 patients and 5 in healthy subjects were positive. The statistical comparison of the amount of positive biomarker was performed in two groups and it was shown that there is a statistically significant difference between these two groups (P<0.001).

This study showed that miR155 gene and CEA and VEGF proteins are relatively good markers for the diagnosis of non-small cell lung cancer patients in Iranian population.

 Polycystic ovary syndrome (PCOS) is a complex condition that can have various symptoms and complications, one of which is infertility. Dysregulation of miRNA has been associated with the pathogenesis of numerous illnesses such as PCOS. In this study, we evaluated the effect of photobiomodulation therapy (PBMT) and exosome therapy (EXO) on the regulation of miRNA and nucleus acetylation in a PCOS oocyte.

 In this research, 36 oocytes were divided into three groups: control, EXO, and PBM (Wavelength of 640 nm). Subsequently, in-vitro maturation (IVM) was evaluated. Real-time PCR was used to evaluate miRNA-21,16,19,24,30,106,155 and GAPDH. Afterward, oocyte glutathione (GSH) and nucleus acetylation were measured by H4K12.

 The expression of the miR-16, miRNA-19, miRNA-24, miRNA-106 and miRNA-155 genes in the EXO and PBMT groups was significantly down-regulated in comparison to the control group, but the expression of miRNA-21 and miR-30 significantly increased in the EXO and PBMT groups in comparison to the control group. The EXO and PBMT significantly increased GSH and nucleus acetylation (P<0.0001).

 The results of this study showed that the use of EXO and PBMT can improve GSH and nucleus acetylation in the PCOS oocyte and also change the expression of miRNAs.

Valproic acid (VPA) is a commonly used drug for treating epilepsy and other neurological and psychiatric disorders. Drug-induced liver injury (DILI) caused by VPA has been reported in several studies. MicroRNAs (miRNAs) are recognized as potent regulators involved in many biological processes and are currently considered promising biomarkers for detecting DILI. The aim of the present study was to evaluate the expression levels of two hepato-specific microRNAs, miR-122 and miR-155, in hepatocytes exposed to VPA. This study was conducted using HepG2 cell lines treated with different concentrations of VPA for 24, 48, 72, 96, and 120 hours. The results showed that exposure to VPA significantly elevated the transcription levels of both tested miRNAs in HepG2 cell lines after 24 hours. However, prolonged exposure down-regulated the expression levels of these miRNAs, possibly due to VPA-induced cell death. We suggest that the significant decrease in miRNA expression in treated cells is correlated with VPA-induced apoptosis, followed by enhanced cell death after 120 hours of VPA exposure. Our findings imply that miR-122 and miR-155 play an important role in valproic acid detoxification and have prognostic or therapeutic implications.

Pulmonary artery hypertension (PAH) is a devastating syndrome. Our previous studies showed that perillyl alcohol (P), berberine (B) and quercetin (Q) improve PAH. In this study, we investigated the effects of sub-effective doses of these derivatives in double and triple combination forms on PAH in rats. Forty nine rats were divided into seven groups (n=7): 1) control, 2) monocrotaline (MCT), 3) MCT+vehicle (veh), 4) MCT+BP, 5) MCT+PQ, 6) MCT+BQ, and 7) MCT+BPQ. After three weeks of PAH induction with MCT (60 mg/kg), either vehicle (ethanol 5% in saline) or one of the above combinations (dose of 20 mg/kg for B, and doses of 20 and 10 mg/ kg for P and Q in vehicle) was administered for three weeks. Right ventricular (RV) pressure, contractility indices, lung pathology, miR-204 expression, oxidative stress markers, inflammation and apoptosis were assayed. MCT increased RV systolic pressure and hypertrophy, and lung arteriole wall thickness, fibrosis and leukocyte infiltration in the MCT group compared to the CTL group. All treatments improved these effects significantly. Furthermore, MCT reduced antioxidant factors, Bax, P21 and miR-204 expression and increased Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6) and Bcl-2. All of these effects were recovered by combination treatments. The results showed that combination therapy with sub-effective/ineffective doses of these compounds had ameliorative effects against PAH.

Diminished ovarian reserve (DOR) is a condition that affects fertility by reducing the reproductive potential of the ovary. The altered expression profile of cumulus cells (CCs) can negatively affect the quality and quantity of oocytes in the ovaries. Recent studies suggest that circulating miRNAs play a significant role in the ovary function, and their serum expression changes can be valuable biomarkers for predicting ovarian function.

Investigating the expression levels of circulating miRNA-4463 and its target cytochrome P450 19A1 gene (CYP19A1) in DOR-CCs in order to find a molecular pathway involved in DOR.

In this case-control study, a total of 20 DOR-women and 20 women with normal ovarian reservation aged between 20-34 yr referred to Yazd Reproductive Science Institute, Yazd, Iran were included in the study. Serum and CCs were collected, and real time-polymerase chain reaction was performed to investigate the expression level of miR-4463, and its target gene CYP19A1.

Our results showed an inverse relationship between miR-4463 and CYP19A1 expression levels. Therefore, the increase in the expression of miR-4463 was significantly evident in DOR-women compared to the control group (p = 0.0019), while the expression of its target gene, CYP19A1, has significantly decreased in these women (p = 0.001).

The present study suggests that miR-4463 and CYP19A1 pathways could be regulate ovary function. Therefore, examination of this miRNA could be a promising parameter for predicting ovarian reserve and their response to stimulation protocols.

The current research examines the molecular terrain of celiac disease (CD) through microRNA and cytokines as potential new diagnostic and therapeutic markers. Gluten-appropriate immune response is a key feature of an autoimmune clinical entity known as CD that leads to inflammation and degeneration of small intestine mucosa. However, the mechanisms responsible for this remain unclear.

Quantitative reverse transcription polymerase chain reaction  (RT-qPCR ) was carried out on serum samples obtained from patients with CD and control groups to unravel their pathogenesis. Assessing miR-155, miR-15b, IL-2, IL-7, IL-35and IL-37 levels in expression might be useful in diagnosing or treating the disorder.

A significant dysregulation of these molecular players in patients with CD compared with healthy controls has been evidenced by results from this study. For instance, miR-155 was up-regulated, whereas miR-15b was significantly down-regulated in CD, illustrating their roles in immune responses and inflammation-mediated processes. Besides, there was an over-expression of IL-2 and an under-expression of IL-37 in patients with CD, indicating these biomolecules' role in immuno-dysregulation and inflammatory process underlying CD. In addition, a positive correlation between IL-2 and miRNA 155 expression levels was observed in patients with CD, suggesting that they could be involved together with other cytokines, showing the interplay between immune response pathways and inflammatory cascades during CD pathogenesis.

These molecular signature discoveries might result in new and revolutionary diagnostic modalities and molecular-targeted therapies for CD pathogenesis. When used with the scientific understanding of miRNAs and cytokines associated with CD pathophysiology, it creates a basis for personalized medicine based on the individualized molecular profile of all patients. This will undoubtedly increase the efficacy of CD treatment strategies. In brief, more research on molecular pathways' workings should be done to harness their potential in CD diagnosis and treatment.

The objective of this study was to investigate the correlation between the expression levels of spermmicroRNA-149b and 34c and sperm quality in men diagnosed with oligoasthenoteratozoospermia. In the experimental study, we recruited 30 infertile men with oligoasthenoteratozoospermiaand 30 control samples. In this study, miR-149b and miR 34c expression using reverse transcription polymerase chainreaction (RT-PCR) were evaluated. Semen samples were collected and subjected to initial analysis, including semenparameters, following the protocol provided by the World Health Organization (WHO). The levels of total antioxidantcapacity (TAC) and malondialdehyde (MDA) were measured using an ELISA kit. The expression levels of miR-149b and miR-34c were significantly downregulated in men with oligoasthenoteratozoospermiacompared to age-matched normozoospermic men, as determined by RT-qPCR (P=0.001, andP=0.003 respectively). Correlation analysis revealed a positive correlation between the expression levels of miR-149band miR-34c and various sperm parameters, including sperm count, motility, morphology, viability, sperm mitochondrialmembrane potential, sperm capacity, and TAC. Additionally, an inverse correlation was observed between theexpression levels of miR-149b, miR-34c, DNA fragmentation, and MDA levels. The findings of this study indicate that the decreased expression of miR-149b and miR-34c is associatedwith oligoasthenoteratozoospermia, potentially affecting fundamental semen parameters. These results provide a basisfor future research aimed at exploring potential therapeutic interventions for male infertility.

Oral squamous cell carcinoma is a multifactorial disease that is the sixth most common cancer worldwide. MicroRNAs have been confirmed to play a role in oral squamous cell carcinoma, acting as either oncogenes or tumor suppressor genes. This study examined the expression level and role of microR-148 and microR-375 in oral cancer.

In this study, we used 30 cancer samples with infection and 30 cancer samples without infection. To analyze the expression of microRNA 375 and microRNA 148, we used real-time PCR. First, we extracted total RNA from the samples. Then, we generated cDNA from it. Finally, the obtained cDNA was used in the real-time PCR technique.

In cancer patients with oral infection, there was an increase in microRNA-148 expression and a decrease in microRNA-375 compared to cancer patients without oral infection.

The downregulation of microRNA-375 and upregulation of microRNA-148 can be utilized as diagnostic biomarkers and prognostic factors in oral cancer.