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Background. This study aims to determine the combined effect of physical activity and the hydroalcoholic extract of palm pollen on the expression of mir-21 and mir-132 in cadmium-induced toxicity in the kidney tissue of male rats. Methods. In this study, 48 adult and healthy male Wistar rats with a weight range of 250 ± 30 grams and 12 weeks of age were randomly divided into 6 groups: 1) control, 2) exercise, 3) cadmium, 4) cadmium + exercise, 5) cadmium + palm 200 + exercise, 6) cadmium + exercise + palm 400. All groups received three milligrams per kilogram of body weight of cadmium chloride daily by gavage, and palm pollen extract was injected intraperitoneally with doses of 200 and 400 mg of body weight. Aerobic training started with rats running on a treadmill at a speed of 27 meters per minute for 16 minutes, and one minute was added to the training every day. Results. The results showed that there is a significant difference in the expression of miR-21 between the groups (P=0.001), with cadmium causing a decrease and aerobic exercise and receiving palm pollen extract leading to a significant increase in the miR-21 gene expression (P=0.005). Also, there is a significant difference in the expression of miR-132 between the groups (P=0.04), indicating that cadmium decreased this variable when compared to the control; however, the combined effect of exercise and palm pollen administration was not statistically significant (P=0.98). Conclusion. Our study showed that performing moderate-intensity regular exercise along with palm pollen in cadmium-treated mice upregulated microRNAs associated with kidney toxicity. Practical Implications. The combined effect of the proposed herbal supplement and physical activity can control the harmful effects of exposure to cadmium on industrial societies and chemical industry workers to some extent.

Alzheimer's disease (AD) affects the elderly population by causing memory impairments, cognitive and behavioral abnormalities. Currently, no curative treatments exist, emphasizing the need to explore therapeutic options that modify the progression of the disease. MicroRNAs (miRNAs), as non-coding RNAs, demonstrate multifaceted targeting potential and are known to be dysregulated in AD pathology. This mini review focuses on two promising miRNAs, hsa-miR-132 and hsa-miR-129, which consistently exhibit differential regulation in AD. By employing computational predictions and referencing published RNA sequencing dataset, we elucidate the intricate miRNA-mRNA target relationships associated with hsa-miR-132 and hsa-miR-129. Our review consistently identifies the downregulation of hsa-miR-132 and hsa-miR-129 in AD brains as a non-coding RNA molecular signature across studies conducted over the past 15 years in AD research. [ABSTRACT FROM AUTHOR]

Background. This study aims to determine the combined effect of physical activity and the hydroalcoholic extract of palm pollen on the expression of mir-21 and mir-132 in cadmium-induced toxicity in the kidney tissue of male rats. Methods. In this study, 48 adult and healthy male Wistar rats with a weight range of 250 ± 30 grams and 12 weeks of age were randomly divided into 6 groups: 1) control, 2) exercise, 3) cadmium, 4) cadmium + exercise, 5) cadmium + palm 200 + exercise, 6) cadmium + exercise + palm 400. All groups received three milligrams per kilogram of body weight of cadmium chloride daily by gavage, and palm pollen extract was injected intraperitoneally with doses of 200 and 400 mg of body weight. Aerobic training started with rats running on a treadmill at a speed of 27 meters per minute for 16 minutes, and one minute was added to the training every day. Results. The results showed that there is a significant difference in the expression of miR-21 between the groups (P=0.001), with cadmium causing a decrease and aerobic exercise and receiving palm pollen extract leading to a significant increase in the miR-21 gene expression (P=0.005). Also, there is a significant difference in the expression of miR-132 between the groups (P=0.04), indicating that cadmium decreased this variable when compared to the control; however, the combined effect of exercise and palm pollen administration was not statistically significant (P=0.98). Conclusion. Our study showed that performing moderate-intensity regular exercise along with palm pollen in cadmium-treated mice upregulated microRNAs associated with kidney toxicity. Practical Implications. The combined effect of the proposed herbal supplement and physical activity can control the harmful effects of exposure to cadmium on industrial societies and chemical industry workers to some extent. [ABSTRACT FROM AUTHOR]

Aim To investigate the effect of CDR132L (miR-132 antisense oligonucleotide) on vascular remodeling and function in mice with hypertension and hyperlipidemia, and explore its possible mechanism. Methods A total of 30 8-week-old male C57BL/6 mice were randomly divided into three groups: control group, model group and CDR132L group, with 10 mice in each group. The control group received with a standard diet while the model group and CDR132L group received N-nitro-L-arginine methyl ester (L-NAME) and high-fat diet to induce hypertension and hyperlipidemia. The CDR132L group was administered with intraperitoneal injection of CDR132L at a dose of 20 mg/kg once weekly for six consecutive weeks, whereas the control group and the model group were given intraperitoneal injection of an equivalent volume of normal saline. The tail-cuff method was utilized for blood pressure measurement, blood lipid and glucose levels were assayed by an automatic biochemical analyzer, the thoracic aorta structure was observed by HE staining, endothelium-dependent relaxation of the thoracic aorta was evaluated by the vascular ring test, the expression level of miR-132 in the thoracic aorta was measured by qPCR, the protein expression levels of Gab1 and endothelial nitric oxide synthase (eNOS) in the thoracic aorta were determined by Western blot. Results Compared with the control group, the model group demonstrated notable rises in systolic and diastolic blood pressure, serum triglyceride, total cholesterol levels, and body weight. Moreover, the intima of thoracic aorta and the thickness of vascular wall was uneven, the smooth muscle cells of the tunica media were arranged irregularly, with a large amount of fat deposition in the vascular wall, and the endothelium-dependent relaxation response of thoracic aorta was decreased (P<0. 05). The expression level of miR-132 in the thoracic aorta was significantly increased (P<0. 05), while the expression level of Gab1 and eNOS protein was markedly decreased (P<0. 05). Compared with the model group, the CDR132L group showed no significant differences in systolic and diastolic blood pressure, serum triglyceride and total cholesterol levels, as well as body weight (P>0. 05). However, the CDR132L group exhibited a complete and smooth intima of the thoracic aorta with minimal intravascular lipid deposition, the thickness of the vascular wall was uniform, the smooth muscle cells of the tunica media were arranged orderly, accompanied by enhanced endothelium-dependent relaxation response of the thoracic aorta (P<0. 05). The expression level of miR-132 in the thoracic aorta was significantly decreased (P <0. 05), while the expression levels of Gab1 and eNOS protein were significantly increased (P<0. 05). Conclusion CDR132L can improve vascular remodeling and endothelium-dependent relaxation in hypertensive and hyperlipidemia mice, which may be related to the decrease of miR-132 expression level and the up-regulation of Gab1 and eNOS protein expression levels in the thoracic aorta. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) affects the elderly population by causing memory impairments, cognitive and behavioral abnormalities. Currently, no curative treatments exist, emphasizing the need to explore therapeutic options that modify the progression of the disease. MicroRNAs (miRNAs), as non-coding RNAs, demonstrate multifaceted targeting potential and are known to be dysregulated in AD pathology. This mini review focuses on two promising miRNAs, hsa-miR-132 and hsa-miR-129, which consistently exhibit differential regulation in AD. By employing computational predictions and referencing published RNA sequencing dataset, we elucidate the intricate miRNA-mRNA target relationships associated with hsa-miR-132 and hsa-miR-129. Our review consistently identifies the downregulation of hsa-miR-132 and hsa-miR-129 in AD brains as a non-coding RNA molecular signature across studies conducted over the past 15 years in AD research.

Abstract Backgrounds Developed countries have a high mortality rate from atherosclerosis and are frequently linked to inflammation and other blood lipid disorders. MicroRNA expression can affect atherosclerotic plaque formation, lipid metabolism, inflammation, and other related processes. The search aimed to determine whether microRNA-138-5p or microRNA-132-3p expression levels are related to patient atherogenic genes. Methods Angiographic diagnostic method was used to select 45 healthy samples and 45 atherosclerosis patients, along with the laboratory and demographic information. After isolating peripheral blood mononuclear cells (PBMCs) from blood, the levels of miR-138 and miR-132 and the relative expression of Sirtuin 1 (SIRT1), signal transducer and activator of transcription-3 (STAT3), and CD36 genes measured using real-time PCR. Results miR-138 was upregulated compared to the control group in the atherosclerosis patient group (P

Backgrounds: Developed countries have a high mortality rate from atherosclerosis and are frequently linked to inflammation and other blood lipid disorders. MicroRNA expression can affect atherosclerotic plaque formation, lipid metabolism, inflammation, and other related processes. The search aimed to determine whether microRNA-138-5p or microRNA-132-3p expression levels are related to patient atherogenic genes. Methods: Angiographic diagnostic method was used to select 45 healthy samples and 45 atherosclerosis patients, along with the laboratory and demographic information. After isolating peripheral blood mononuclear cells (PBMCs) from blood, the levels of miR-138 and miR-132 and the relative expression of Sirtuin 1 (SIRT1), signal transducer and activator of transcription-3 (STAT3), and CD36 genes measured using real-time PCR. Results: miR-138 was upregulated compared to the control group in the atherosclerosis patient group (P < 0.05). In contrast, SIRT1 was downregulated in patients (P < 0.05). Our results also showed that the expression levels of miR-138 can use as a biomarker for atherosclerosis detection (P < 0.05). In addition, the expression of miR-138 with SIRT1 had a significant negative correlation (P < 0.05), and miR-132 was directly correlated with STAT3 (P < 0.01). Interestingly, STAT3 was negatively correlated with SIRT1 (P < 0.05) and positively with CD36 (P < 0.01). Conclusion: Since atherosclerosis has no specific clinical symptoms and early diagnosis is vital, the use of miR-138 diagnostic biomarkers can play an essential role in early diagnosis. Furthermore, this study highlights the overlap of SIRT1-STAT3-CD36 signaling pathways with miR-132 and miR-138 in atherosclerosis. [ABSTRACT FROM AUTHOR]

UCA1 is predicted to bind to miR-132, which is a key player in the proliferation of vascular smooth muscle cells (VSMCs). This research studied the role of lncRNA UCA1 in atherosclerosis. The binding of UCA1 to miR-132 was proved by dual luciferase activity assay and RNA immunoprecipitation. UCA1 and miR-132 failed to affect each other’s expression in VSMCs. UCA1 was upregulated and miR-132 was decreased in atherosclerosis plasma. However, they are not closely correlated across atherosclerosis and control plasma sample. Interestingly, UCA1 suppressed the role of miR-132 in downregulating Lrrfip1 expression and promoting VSMC proliferation. Therefore, UCA1 is downregulated in atherosclerosis and may regulate miR-132/Lrrfip1 axis to promote VSMC proliferation.

The rapid increase in urbanization is altering the natural composition of the day–night light ratio. The light/dark cycle regulates animal learning, memory, and mood swings. A study was conducted to examine the effect of different quantity and quality of light at night on the daily clock, learning, memory, cognition, and expression of transcripts in key learning centers. Treatment was similar for experiments one to three. Rats were exposed for 30 days to 12 h light and 12 h dark with a night light of 2 lx (dLAN group), 250 lx (LL), or without night light (LD). In experiment one, after 28 days, blood samples were collected and 2 days later, animals were exposed to constant darkness. In experiment two, after 30 days of treatment, animals were subjected to various tests involving learning, memory, and cognition. In experiment three, after 30 days of treatment, animals were sampled, and transcript levels of brain-derived neurotrophic factor, tyrosine kinase, Growth-Associated Protein 43, Neurogranin, microRNA-132, cAMP Response Element-Binding Protein, Glycogen synthase kinase-3β, and Tumor necrosis factor α were measured in hippocampus, thalamus, and cortex tissues. In experiment four, animals were exposed to night light of 0.019 W/m2 but of either red (640 nm), green (540 nm), or blue (450 nm) wavelength for 30 days, and similar tests were performed as mentioned in experiment 2. While in experiment five, after 30 days of respective wavelength treatments, all animals were sampled for gene expression studies. Our results show that exposure to dLAN and LL affects the daily clock as reflected by altered melatonin secretion and locomotor activity, compromises the learning, memory, and cognitive ability, and alterations in the expression levels of transcripts in the hypothalamus, cortex, and thalamus. The effect is night light intensity dependent. Further, blue light at night has less drastic effects than green and red light. These results could be of the potential use of framing the policies for the use of light at night. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) a phenolic compound originally derived from the turmeric plant is known as a promising therapeutic agent for several human diseases including malignancies. Despite remarkable anti-cancer effects, disadvantages including short half-life time and low bioavailability limit its usage for efficient cancer therapy. Curcumin was first encapsulated into PLGA-PEG nanoparticles. Then, using DLS, FE-SEM, and FTIR assays, the synthesized NPs were characterized. Furthermore, MCF-7 cells were exposed to different concentrations of free CUR and NP-CUR, and then the cell survival rates and gene expression profile were followed utilizing the MTT and qRT-PCR techniques, respectively. The obtained results illustrated that CUR was efficiently encapsulated into PLGA-PEG NPs. Also, MTT assay indicated that NP-curcumin more effectively inhibited MCF-7 cell viability than free curcumin treatment. Besides, qRT-PCR results evidenced that exposure of cells to CUR and NP-CUR led to upregulation of P53 and miR-132, and subsequent downregulation of hTRET and Cyclin D1 genes expression. However, changes in the expression profiles of these genes were remarkably higher in NP-CUR group. Taken together, the findings of this study suggested that encapsulation of curcumin into PLGA-PEG could increase its anti-cancer effects on breast cancer cells by modulating P53, Cyclin D1, hTRET, and MicroRNA-132 axis. [ABSTRACT FROM AUTHOR]

Obesity has now surpassed malnutrition and infectious diseases as the most significant contributor to health problems worldwide. In particular, obesity is associated with several metabolic disorders, including hyperlipidemia, hepatic steatosis, and subfertility. Genipin (GNP), the aglycone of geniposide, is isolated from the extract of the traditional Chinese medicine Gardenia jasminoides Ellis and has been used in traditional oriental medicine against several inflammation-driven diseases. However, the effect and molecular mechanism of GNP on obesity-associated dyslipidemia and sperm dysfunction still need to be explored. In this study, we detect the effects of GNP on hyperlipidemia, hepatic lipid accumulation and sperm function using a high-fat diet (HFD)-induced obese mouse model. We find that obese mice treated with GNP show an improvement in body weight, serum triglyceride levels, serum hormone levels, serum inflammatory cytokines, hepatic steatosis and sperm function. At the molecular level, HFD/GNP diversely regulates the expression of miR-132 in a tissue-specific manner. miR-132 further targets and regulates the expression of SREBP-1c in liver cells, as well as the expressions of SREBP-1c and StAR in Leydig cells in the testis, thus modifying lipogenesis and steroidogenesis, respectively. Collectively, our data demonstrate that GNP shows a broad effect on the improvement of HFD-induced metabolic disorder and sperm dysfunction in male mice by tissue-specific regulation of miR-132. Our findings reveal the function GNP in ameliorating hepatic lipid metabolism and sperm function and suggest that this compound is a versatile drug to treat metabolic disorders.

The tissue reconstruction of diabetic wounds mainly depends on the proliferation and remodelling of cutaneous cells around wounds and the transplantation of random skin flaps, however, the proliferation of cells or survival of skin flaps are difficult due to the severe inflammation and other problems caused by diabetes. The stem cell-derived exosomes loaded with miRNA can be an effective therapeutic strategy for promoting diabetic wound healing. Therefore, in this study, the engineered exosomes derived from miR-132-overexpressing adipose stem cells (miR-132-exo) was obtained for promoting the healing of diabetic wounds and skin flaps. In vitro, the miR-132-exo promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). In vivo, streptozotocin (STZ) induced diabetic mice were used to create full-thickness skin wounds and random skin flaps to further investigate the healing effect of miR-132-exo. The results showed miR-132-exo evidently enhanced the survival of skin flaps and promote diabetic wound healing, through reducing local inflammation, promoting angiogenesis and stimulating M2-macrophages polarization mediated by NF-κB signaling pathway. These novel findings demonstrated that engineered miR-132-exo can be a potent therapeutic for treating diabetic wounds and inflammatory-related disease.

UCA1 is predicted to bind to miR-132, which is a key player in the proliferation of vascular smooth muscle cells (VSMCs). This research studied the role of lncRNA UCA1 in atherosclerosis. The binding of UCA1 to miR-132 was proved by dual luciferase activity assay and RNA immunoprecipitation. UCA1 and miR-132 failed to affect each other’s expression in VSMCs. UCA1 was upregulated and miR-132 was decreased in atherosclerosis plasma. However, they are not closely correlated across atherosclerosis and control plasma sample. Interestingly, UCA1 suppressed the role of miR-132 in downregulating Lrrfip1 expression and promoting VSMC proliferation. Therefore, UCA1 is downregulated in atherosclerosis and may regulate miR-132/Lrrfip1 axis to promote VSMC proliferation. [ABSTRACT FROM AUTHOR]

Betanin (BET) has been studied for its therapeutic benefits in various diseases, but its low bioavailability and uncertain brain penetration limit its efficacy. Accordingly, this study aimed to explore BET-loaded liposomal nanocarriers (LPN) as a novel treatment for Alzheimer's disease (AD), focusing on the triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways implicated in AD. In an AlCl 3 -induced AD rat model, 48 male Wistar rats were divided into four groups: control, AlCl 3 (50 mg/kg, intraperitoneal), AlCl 3 +BET (100 mg/kg, per os), and AlCl 3 +BET LPN (25 mg/kg, intranasally), with treatments administered for 28 days. Morris water maze test and histopathological examination showed that BET LPN-treated rats had improved spatial and learning memory and less hippocampal and cortical degeneration compared with the AlCl 3 and oral BET groups. Mechanistically, BET LPN treatment corrected AD biomarkers, increased miR-132 and ADAM10 expression, and reduced oxidative stress, inflammation, and apoptosis. Additionally, BET LPN treatment suppressed the expression of TREM2, DAP12, ERK1/2, and mitogen-activated protein kinase 1/2 (MEK1/2), showing greater improvement than oral BET. These findings suggest that BET LPN enhances cognitive function and neuroprotection in AD by modulating miR-132 and ADAM10 and inhibiting ERK1/2 and TREM2/DAP12 pathways, providing a more effective treatment compared with traditional oral BET administration., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Objective To investigate the effect of notoginseng saponin R1 (NGR1)on the expression of miR-132 in human hypopharyngeal squamous cell carcinoma cell line FaDu, and to explore its possible anti-tumor mechanism. Methods FaDu cells were treated with 0, 75, 150 and 300 µmol/L NGR1, and were labeled as the Control group, 75 µmol/L NGR1 group, 150 µmol/L NGR1 group and 300 µmol/L NGR1 group, respectively. The proliferation ability of cells in each group was detected by MTT assay, and the relative expression of miR-132 in each group was detected by real-time PCR. FaDu cells were further divided into the Control group (no treatment), NGR1 group (given 150 µmol/L NGR1), miR-132 inhibitor-NC group (transfected with miR-132 inhibitor-NC), miR-132 inhibitor group (transfected with miR-132 inhibitor), miR-132 inhibitor-NC+NGR1 group (150 µmol/L NGR1 treatment after transfection with inhibitor-NC), and miR-132 inhibitor+NGR1 group (150 µmol/L NGR1 treatment after transfection with inhibitor), respectively. MTT, Scratch and Transwell invasion assays were used to detect the effects of inhibition or up-regulation of miR-132 on the proliferation, migration and invasion abilities of FaDu cells. Results The proliferation abilities of FaDu cells in the Control group, 75 µmol/L NGR1 group, 150 µmol/L NGR1 group and 300 µmol/L NGR1 group decreased successively, and the relative expression of miR-132 in FaDu cells increased successively, and the differences were statistically significant (all P<0. 05). Compared with Control group, the viability, migration and invasion abilities of FaDu cells in the miR132 inhibitor group were enhanced, and the viability, migration and invasion abilities of FaDu cells in the NGR1 group were weakened (all P<0. 05). Compared with the NGR1 group, the viability, migration and invasion of FaDu cells in miR-132 inhibitor+NGR1 group significantly increased (all P<0. 05). Conclusion NGR1 may inhibit the proliferation, migration and invasion of FaDu cells by up-regulating the expression of miR-132. [ABSTRACT FROM AUTHOR]

Objective To investigate the preventive effect of miR-132 on sevoflurane-induced cognitive dysfunction in newborn mice and its possible mechanism. Methods Sixty-four SPF healthy male 6-day-old C57BL/6 mice were ran‐ domly divided into four groups：normal control group(group A), sevoflurane group(group B), sevoflurane+agomir-NC group(Group C), and sevoflurane+agomir-132 group(Group D), with 16 mice in each group. Except for group A, mice in the other three groups all inhaled 4% sevoflurane continuously for 4 h to induce mouse cognitive dysfunction models. The lateral ventricle of mice in the group C and group D was injected with agomir-NC and agomir-132, respectively, be‐ fore modeling, and mice in the group A and group B with equal volume of normal saline. At 24 h after sevoflurane induc‐ tion, 8 mice in each group were randomly selected to obtain hippocampal tissues. The expression of miR-132 in hippocam‐ pal tissues of mice in each group was detected by qRT-PCR, the expression of HMGB1, Bax and Bcl-2 protein in hippo‐ campal tissues of mice in each group was detected by Western blotting, and the levels of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyd(MDA)in hippocampus were detected by ELISA. The remaining 8 mice in each group underwent the Morris water maze test to test their neurocognitive function at the sexual maturity stage. Results Compared with group A, the relative expression of miR-132 in the hippocampus of groups B, C, and D all decreased(all P<0. 05)；there was no significant difference in the relative expression of miR-132 in the hippocampus between the group B and group C(P> 0. 05). Compared with group B and group C, the relative expression of miR-132 in the hippocampus of group D increased (P<0. 05). Compared with group A, the escape latency and swimming distance of groups B, C and D increased(all P< 0. 05), and the stay time in the original platform quadrant and the number of times of crossing the original platform position decreased(all P<0. 05)；there was no significant difference in the above indexes between the group B and group C(all P> 0. 05). Compared with group B and group C, the escape latency and swimming distance of group D were shortened(all P< 0. 05), and the stay time in the original platform quadrant and the number of times of crossing the original platform position increased(all P<0. 05). Compared with group A, the expression of HMGB1 protein and the levels of inflammatory factors such as IL-1β, TNF-α, and IL-6 in the hippocampus of groups B, C, and D all increased(all P<0. 05)；there was no sig‐ nificant difference between the group B and group C(all P>0. 05). Compared with group B and group C, the expression of HMGB1 protein and the levels of inflammatory factors such as IL-1β, TNF-α, and IL-6 in the hippocampus of group D de‐ creased(all P<0. 05). Compared with group A, the levels of SOD, GSH-PX and Bcl-2 protein in hippocampus of groups B, C and D decreased(all P<0. 05), while the levels of MDA and Bax protein increased(all P<0. 05)；no significant dif‐ ferences were found in the above indexes between group B and group C(all P>0. 05). Compared with group B and group C, the levels of SOD, GSH-PX and Bcl-2 protein in hippocampus of group D increased(all P<0. 05), while the levels of MDA and Bax protein decreased(all P<0. 05). Conclusion MiR-132 can prevent sevoflurane-induced cognitive dys‐ function in newborn mice. The mechanism may be that miR-132 reduces the release of inflammatory factors, oxidative stress and apoptosis by inhibiting the expression of HMGB1 gene. [ABSTRACT FROM AUTHOR]

Abstract Cancer as one of the leading causes of human deaths has always been one of the main health challenges in the world. Despite recent advances in therapeutic and diagnostic methods, there is still a high mortality rate among cancer patients. Late diagnosis is one of the main reasons for the high ratio of cancer related deaths. Therefore, it is required to introduce novel early detection methods. Various molecular mechanisms are associated with the tumor progression and metastasis. MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) family that has important functions in regulation of the cellular processes such as cell proliferation, apoptosis, and tumor progression. Moreover, they have higher stability in body fluids compared with mRNAs which can be introduced as non-invasive diagnostic markers in cancer patients. MiR-132 has important functions as tumor suppressor or oncogene in different cancers. In the present review, we have summarized all of the studies which have been reported the role of miR-132 during tumor progressions. We categorized the miR-132 target genes based on their cell and molecular functions. Although, it has been reported that the miR-132 mainly functions as a tumor suppressor, it has also oncogenic functions especially in pancreatic tumors. MiR-132 mainly exerts its roles during tumor progressions by regulation of the transcription factors and signaling pathways. Present review clarifies the tumor specific molecular mechanisms of miR-132 to introduce that as an efficient non-invasive diagnostic marker in various cancers.

Eukaryotic gene expression is controlled at multiple levels, including gene transcription and protein translation initiation. One molecule with key roles in both regulatory mechanisms is methyl CpG binding protein 2 (MeCP2). MECP2 gain- and loss-of-function mutations lead to Rett Syndrome and MECP2 Duplication Syndrome, respectively. To study MECP2 gain-of-function, we generated stably transduced human brain cells using lentiviral vectors for both MECP2E1 and MECP2E2 isoforms. Stable overexpression was confirmed by Western blot and immunofluorescence. We assessed the impact of MeCP2E1-E2 gain-of-function on the MeCP2 homeostasis regulatory network (MECP2E1/E2-BDNF/BDNF-miR-132), mTOR-AKT signaling, ribosome biogenesis, markers of chromatin structure, and protein translation initiation. We observed that combined co-transduction of MeCP2 isoforms led to protein degradation of MeCP2E1. Proteosome inhibition by MG132 treatment recovered MeCP2E1 protein within an hour, suggesting its induced degradation through the proteosome pathway. No significant change was detected for translation initiation factors as a result of MeCP2E1, MeCP2E2, or combined overexpression of both isoforms. In contrast, analysis of human Rett Syndrome brains tissues compared with controls indicated impaired protein translation initiation, suggesting that such mechanisms may have differential sensitivity to MECP2 gain- and loss-of-function. Collectively, our results provide further insight towards the dose-dependent functional role of MeCP2 isoforms in the human brain. [ABSTRACT FROM AUTHOR]

Abstract Background Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the functions of miRNA-132 (miR-132) in the modulation of PTEN/PI3K/AKT signaling pathway in the development and progression of osteoarthritis. Methods Eight male osteoarthritic patients and eight healthy males were recruited. Male Sprague Dawley (SD) rats were used for cellular experiments. QRT-PCR was performed to detect the expression levels of miR-132, PTEN, PI3K and AKT. MTT assay and apoptosis assay were carried out to measure the cell proliferation rate and cell apoptosis rate, respectively. Western blotting was employed to detect the protein expression of related RNAs and inflammatory factors. Results In osteoarthritic patients, the expression level of miR-132 was decreased, compared with that in the normal group. Over-expression of miR-132 elevated cell proliferation and decreased apoptosis of chondrocytes. Down-regulation of miR-132 decreased cell proliferation and induced apoptosis in chondrocytes. In addition, down-regulation of miR-132 promoted the expression of Bax protein and activated caspase-3/9, increased inflammation divisors. PTEN inhibitor antagonized the destructive effect of the miR-132 inhibitor on cell proliferation of chondrocytes. PI3K inhibitor increased the destructive effect of the miR-132 inhibitor on osteoarthritis. Conclusion In conclusion, miR-132 is an important regulator of osteoarthritis in chondrocytes through the PTEN/PI3K/AKT signaling pathway.

Background The long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) has been verified as a crucial regulator in many types of tumours but not clear in cervical cancer (CC). This study aims to investigate the effect and further mechanisms of lncRNA SNHG5 in CC. Methods The expression of SNHG5 and miR-132, as well as SOX4 (sex-determining region Y-box 4) mRNA expression were determined by quantitative real-time PCR (qRT-PCR). The protein level of SOX4 and epithelial-mesenchymal transition (EMT)-related proteins were evaluated by western blot. Then, Edu and Transwell assay were performed to assess the proliferation, migration and invasion of CC cells. RNA immunoprecipitation (RIP) and RNA pull-down assay were conducted to explore the relationship between SNHG5 and miR-132. Results SNHG5 and SOX4 were upregulated, and miR-132 was downregulated in CC tissues and cell lines. SNHG5 was positively correlated with FIGO stage (p = .003) and lymph node metastasis (p = .001). Pearson’s correlation analysis conveyed that SNHG5 was positively correlated with SOX4, and miR-132 was negatively correlated with SOX4 and SNHG5. Knockdown of SNHG5 in vitro reduced CC cell proliferation, migration and invasion through regulating miR-132. Moreover, overexpression of miR-132 restrained CC cell proliferation, migration, and invasion through targeting SOX4, and SNHG5 enhanced SOX4 expression via negatively regulating miR-132. Conclusion SNHG5 promotes SOX4 expression to accelerate CC cell proliferation, migration and invasion through negatively regulating miR-132.

Alterations in the neuro-immune balance play a major role in the pathophysiology of chronic neuropathic pain. MicroRNAs (miRNA) can regulate both immune and neuronal processes and may function as master switches in chronic pain development and maintenance. We set out to analyze the role of miR-132-3p, first in patients with peripheral neuropathies and second in an animal model of neuropathic pain. We initially determined miR-132-3p expression by measuring its levels in white blood cells (WBC) of 30 patients and 30 healthy controls and next in sural nerve biopsies of 81 patients with painful or painless inflammatory or non-inflammatory neuropathies based on clinical diagnosis. We found a 2.6 fold increase in miR-132-3p expression in WBC of neuropathy patients compared to healthy controls (p

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes. [ABSTRACT FROM AUTHOR]

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents. [ABSTRACT FROM AUTHOR]

Abstract Background Non-invasive diagnostic markers are of great importance for early screening nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) play significant roles in many metabolic disease, including NAFLD. Therefore, this study focusd on a Chinese population to explore the possible correlation between circulating miR-132 and NAFLD. Results Serum miR-132 was positively associated with NAFLD in non-type 2 diabetes mellitus (T2DM) groups by logistic regression (OR = 3.082 [1.057, 8.988], P = 0.039) after adjusting age, sex, and body mass index (BMI). Additionally, in non-T2DM subgroup, after adjusting age, sex, bmi, serum miR-132 was significantly associated with ALT (β ± SE = 0.005 ± 0.002, P = 0.018), TG (β ± SE = 0.072 ± 0.029, P = 0.015), FPG (β ± SE = 0.123 ± 0.058, P = 0.036), γ-GT (β ± SE = 0.002 ± 0.001, P = 0.047), apoE (β ± SE = 0.038 ± 0.002, P = 0.017) . Conclusions Serum miR-132 was found to be associated with NAFLD risk in a Chinese cross-section study. This finding provides a prospective research direction for early screening and diagnosing NAFLD.

Abstract Background and Aims To evaluate the expression of microRNA 132 (miR‐132) in fetuses with normal growth and in fetuses with late‐onset growth restriction (FGR). Methods In a prospective cohort study, 48 fetuses (24 with late‐onset FGR and 24 with normal growth) were scanned with Doppler ultrasound after 34 weeks to measure the umbilical artery and middle cerebral artery pulsatility indices and followed until birth. Subsequently, blood samples from the umbilical cord were collected to evaluate the expression of miR‐132 by means of Real‐time quantitative polymerase chain reaction, determining the existence of normality cut‐offs and associations with birth weight (BW) centile, cerebroplacental ratio multiples of the median (CPR MoM), and intrapartum fetal compromise (IFC). Results In comparison with normal fetuses, late‐onset FGR fetuses showed upregulation of miR‐132 (33.94 ± 45.04 vs. 2.88 ± 9.32 2−ddCt, p

Purpose. The aim of the study was to investigate whether the circulating miR-132, miR-146a, miR-222, and miR-320 levels are used in the differential diagnosis of women with polycystic ovary syndrome (PCOS) and healthy women. Methods. This prospective case-control study included 50 women with PCOS and age- and body mass index- matched 50 healthy controls. The hormone and lipid profiles, levels of microRNAs (miRNAs), and parameters of carbohydrate metabolism were measured. Results. Expression levels of miRNAs were assessed using the two-step quantitative real-time polymerase chain reaction. Circulating miR-132, miR-146a and miR- 222 levels were significantly downregulated in the PCOS group compared with the control group. The miR-320 levels did not differ between the two groups. Free testosterone was negatively correlated with miR-132, miR-146a and miR-222. Insulin was negatively correlated with miR-132 and miR-146a. Conclusions. The results of the study revealed that miRNA expression, may suggest a possible distinction between healthy women and PCOS patients. miR-132, miR-146a, and miR-222 may have key functions in the pathogenesis of PCOS. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is an age-related neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra. LncRNA MIAT has been shown to be critical in Alzheimer's disease, but its role and mechanism in PD are still unknown. Differentiated PC12 cells were treated with 1-methyl-4-phenylpyridinium (MPP+) to establish in vitro cell injury model of PD. MTT, Annexin V-PI double staining test and Western blot were used to detect cell viability and apoptosis. Reactive oxygen species (ROS), superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (GSH-PX) kits were used to evaluate oxidative stress in cells. These results showed that LncRNA MIAT was down-regulated in MPP+-induced PC12 cells. Overexpression of LncRNA MIAT remarkably increased cell viability, inhibited cell apoptosis and oxidative stress in MPP+-treated cells. In addition, we proved that miR-132 is a target of LncRNA MIAT. Overexpression of miR-132 could reverse the positive effect of LncRNA MIAT overexpression on MPP+-induced cell oxidative stress injury. SIRT1 is a target of miR-132 and silencing of SIRT1 attunated the positive effect of LncRNA MIAT overexpression on oxidative stress injury in MPP+-induced PC12 cells. In conclusion, this study indicated that LncRNA MIAT suppressed MPP+-induced oxidative stress injury by regulating miR-132/SIRT1 axis in PC12 cells. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease and subsequent heart failure threaten global health and impose a huge economic burden on society. MicroRNA-132 (miR-132), a regulatory RNA ubiquitously expressed in the cardiovascular system, is up-or down-regulated in the plasma under various cardiac conditions and may serve as a potential diagnostic or prognostic biomarker. More importantly, miR-132 in the myocardium has been demonstrated to be a master regulator in many pathological processes of ischemic or nonischemic heart failure in the past decade, such as myocardial hypertrophy, fibrosis, apoptosis, angiogenesis, calcium handling, neuroendocrine activation, and oxidative stress, through downregulating target mRNA expression. Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease and subsequent heart failure threaten global health and impose a huge economic burden on society. MicroRNA-132 (miR-132), a regulatory RNA ubiquitously expressed in the cardiovascular system, is up-or down-regulated in the plasma under various cardiac conditions and may serve as a potential diagnostic or prognostic biomarker. More importantly, miR-132 in the myocardium has been demonstrated to be a master regulator in many pathological processes of ischemic or nonischemic heart failure in the past decade, such as myocardial hypertrophy, fibrosis, apoptosis, angiogenesis, calcium handling, neuroendocrine activation, and oxidative stress, through downregulating target mRNA expression. Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease.

Abstract During embryonic development, cells differentiate in a coordinated manner, aligning their fate decisions and differentiation stages with those of surrounding cells. However, little is known about the mechanisms that regulate this synchrony. Here we show that cells in close proximity synchronize their differentiation stages and cellular phenotypes with each other via extracellular vesicle (EV)‐mediated cellular communication. We previously established a mouse embryonic stem cell (ESC) line harbouring an inducible constitutively active protein kinase A (CA‐PKA) gene and found that the ESCs rapidly differentiated into mesoderm after PKA activation. In the present study, we performed a co‐culture of Control‐ESCs and PKA‐ESCs, finding that both ESC types rapidly differentiated in synchrony even when PKA was activated only in PKA‐ESCs, a phenomenon we named ‘Phenotypic Synchrony of Cells (PSyC)’. We further demonstrated PSyC was mediated by EVs containing miR‐132. PKA‐ESC‐derived EVs and miR‐132‐containing artificial nano‐vesicles similarly enhanced mesoderm and cardiomyocyte differentiation in ESCs and ex vivo embryos, respectively. PSyC is a new form of cell‐cell communication mediated by the EV regulation of neighbouring cells and could be broadly involved in tissue development and homeostasis.

Our study aimed to explore the function and mechanism of action of long noncoding RNA (lncRNA) SRY-Box 21 antisense RNA 1 (SOX21-AS1) in amyloid beta25–35 (Aβ25–35)-induced neuronal damage. To induce neuronal damage, neuronal cells and differentiated IMR-32 neuroblastoma cells were challenged by Aβ25–35. SOX21-AS1 and miR-132 quantities were detected by quantitative reverse transcription polymerase chain reaction. Cell damage was evaluated by detecting the changes of cell viability, apoptosis, and oxidative stress. Cell viability was measured using cell counting kit-8. Cell apoptosis was evaluated by flow cytometry and caspase-3 activity. The oxidative stress was analyzed by reactive oxygen species level. The expression of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was examined by western blot. SOX21-AS1 abundance was up-regulated in Aβ25–35-challenged neuronal cells. Silencing of SOX21-AS1 attenuated Aβ25–35-induced viability reduction and promotion of apoptosis and oxidative stress, suggesting that silencing of SOX21-AS1 repressed Aβ25–35-induced neuronal damage. miR-132 quantity was reduced in Aβ25–35-challenged neuronal cells, and negatively controlled by SOX21-AS1. miR-132 knockdown abolished the effect of SOX21-AS1 silencing on Aβ25–35-induced neuronal damage, indicating that SOX21-AS1 controls Aβ25–35-induced neuronal damage via regulating miR-132. The PI3K/AKT signaling was repressed in Aβ25–35-challenged cells, but this effect was counteracted upon overexpression of miR-132. In conclusion, SOX21-AS1 knockdown mitigated Aβ25–35-dependent neuronal cell damage by promoting miR-132/PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

During embryonic development, cells differentiate in a coordinated manner, aligning their fate decisions and differentiation stages with those of surrounding cells. However, little is known about the mechanisms that regulate this synchrony. Here we show that cells in close proximity synchronize their differentiation stages and cellular phenotypes with each other via extracellular vesicle (EV)‐mediated cellular communication. We previously established a mouse embryonic stem cell (ESC) line harbouring an inducible constitutively active protein kinase A (CA‐PKA) gene and found that the ESCs rapidly differentiated into mesoderm after PKA activation. In the present study, we performed a co‐culture of Control‐ESCs and PKA‐ESCs, finding that both ESC types rapidly differentiated in synchrony even when PKA was activated only in PKA‐ESCs, a phenomenon we named 'Phenotypic Synchrony of Cells (PSyC)'. We further demonstrated PSyC was mediated by EVs containing miR‐132. PKA‐ESC‐derived EVs and miR‐132‐containing artificial nano‐vesicles similarly enhanced mesoderm and cardiomyocyte differentiation in ESCs and ex vivo embryos, respectively. PSyC is a new form of cell‐cell communication mediated by the EV regulation of neighbouring cells and could be broadly involved in tissue development and homeostasis. [ABSTRACT FROM AUTHOR]

AIM:To analyze the expression and significance of miR-132 in the plasma of patients with diabetic retinopathy.METHODS: From July 2015 to October 2015, a total of 55 patients with diabetes who were treated in our hospital were divided into 5 groups according to diabetic retinopathy clinical staging international standard, including 13 cases of no obvious retinopathy as group A, 10 cases of mild NPDR as group B, 11 cases of moderate NPDR as group C, 12 cases of severe NPDR as group D and 9 cases of PDR as group E, at the same time, the other 12 healthy people were enrolled as control group F. Real-time quantitative PCR(qRT-PCR)technique was used to detect the relative expression of miR-132 in the plasma of 55 patients with different stages of diabetic retinopathy and the expression difference between different groups were compared. RESULTS: Compared with the healthy control group, the expression of miR-132 in the plasma was decreased in other groups(PCONCLUSION: The expression of miR-132 in the plasma of patients with DR was slightly lower in the non-proliferative and proliferative stage than in healthy subjects and background diabetic retinopathy. Furthermore, miR-132 may be a new biomarker for DR.

Post-traumatic stress disorder (PTSD) is usually accompanied by anxiety symptoms and decreased expression of brain-derived neurotrophic factor (BDNF), which played an important role in promoting neuronal proliferation and survival. Methyl CpG-binding protein 2 (MeCP2) is a positive mediator of BDNF and is regulated by miR-132-3p. In the present study, we explored the possible molecular mechanism of miR-132, focusing on the involvement of MeCP2 and BDNF in the formation of anxiety-like symptoms of PTSD. Single prolonged stress (SPS) was used to establish a model of PTSD in adult rats and the anxiety-like behavior was tested by the elevated plus-maze (EPM). The level of miR-132 in the prefrontal cortex (PFC) was increased and intraventricular injection of anti-miR-132 could significantly improve the anxiety-like behavior of rats exposed to SPS through MeCP2 and the subsequent upregulation of BDNF levels. Then tropomyosin-related kinase B (TrkB) and downstream signals, including MAP kinase ERK1/2 and phosphoinositol 3-kinase (PI3K)/Akt pathways, were activated by BDNF upregulation, and might participate in regulating dendritic complexity and the expression of postsynaptic density-95 (PSD95) and synapsin I in the PFC of SPS rats. Furthermore, we found that the apoptosis of cells in PFC induced by SPS procedure could be alleviated by miR-132 inhibition. Our results suggest that miR-132 might be involved in the formation of anxiety-like symptoms of adult rat PTSD models by targeting MeCP2, and this effect is related to BDNF/TrkB and its downstream ERK and Akt signaling pathways.

Alzheimer’s disease (AD) is a common neurodegenerative disease in the elderly and is the most common type of dementia. AD is mostly gradual onset, and involves slow, progressive mental decline, accompanied by personality changes; the incidence of AD gradually increases with age. The etiology of AD is unknown, although it is currently believed to be related to abnormal deposition of amyloid β-protein (Aβ) in the brain, hyperphosphorylation of microtubule-associated protein tau, and the release of various cytokines, complements, activators and chemokines by cells. MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs that regulate gene expression at the post-transcriptional level, and manipulate the functions of intracellular proteins and physiological processes. Emerging studies have shown that miRNA plays an important role in regulating AD-related genes. MiR-132 is known as “NeurimmiR” due to its involvement in numerous neurophysiological and pathological processes. Accumulating pre-clinical results suggest that miR-132 may be involved in the progression of Aβ and tau pathology. Moreover, clinical studies have indicated that decreased circulating miR-132 levels could be used a potential diagnostic biomarker in AD. Here, we review the pathogenic role of miR-132 activity in AD, and the potential of targeting miR-132 for developing future therapeutic strategies.

MicroRNAs are a group of short non-coding RNAs (miRNAs), which are epigenetically involved in gene expression and other cellular biological processes and can be considered as potential biomarkers for cancer detection and support for treatment management. This review aims to amass the evidence to reach the molecular mechanism and clinical significance of miR-132 in different types of cancer. Dysregulation of miR-132 level in various types of malignancies, including hepatocellular carcinoma, breast cancer, colorectal cancer, gastric cancer, lung cancer, prostate cancer, osteosarcoma, pancreatic cancer, and ovarian cancer have reported, significantly decrease in its level, which can be indicated to its function as a tumor suppressor. miR-132 is involved in cell proliferation, migration, and invasion through cell cycle pathways, such as PI3K, TGFβ or hippo signaling pathways, or on oncogenes such as Ras, AKT, mTOR, glycolysis. miR-132 could be potentially a candidate as a valuable biomarker for prognosis in various cancers. Through this study, we proposed that miR-132 can potentially be a candidate as a prognostic marker for early detection of tumor development, progression, as well as metastasis. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of miR-132 on the proliferation and migration of nasopharyngeal carcinoma (NPC) cells by negatively targeting the expression of Kruppel-like factor 7 (KLF7). Methods NPC CNE-2Z cells were divided into blank group, NC group, miR-132 mimics group, KLF7-OE group and miR-132 mimics + KLF7-OE group. The expressions of miR-132 in NPC tissues and cells and normal nasopharyngeal tissues and cells were detected by fluorescence quantitative PCR (qPCR). The expression level of KLF7 protein was detected by Western blot assay. The targeting relationship between KLF7 and miR-132 was predicted and verified by TargetScan website and dual luciferase detection. CCK-8 test and Transwell test were used to detect the proliferation, migration and invasion of CNE-2Z cells. The tumor formation test in nude mice and immunohistochemistry were used to detect the growth of CNE-2Z cells in vivo and the blood vessels in tumor. Results The expression level of miR-132 was decreased in nasopharyngeal carcinoma tissue than that in normal nasopharyngeal tissue, and the expression of KLF7 protein was increased. The expression level of miR-132 was decreased in nasopharyngeal carcinoma CNE-2Z cells than that in normal nasopharyngeal epithelial cells NP69, and the expression of KLF7 protein was increased (P＜0.05). TargetScan prediction and dual luciferase detection showed that KLF7 was the target gene of miR-132. Compared with those in the blank group and NC group, the expression of KLF7 protein, cell proliferation activity at 36, 48 and 60 h, numbers of migration and invasion, tumor volume and microvessel density (MVD) in CNE-2Z cells were significantly decreased in miR-132 mimics group (P＜0.05), while the results were oppositive in KLF7- OE group (P＜0.05). Compared with those in miR-132 mimics group, the expression level of KLF7 protein, cell proliferation activity at 36, 48 and 60 h, numbers of migration and invasion, tumor volume and MVD were significantly increased in miR132 mimics + KLF7-OE group (P＜0.05). Conclusion miR-132 can affect the proliferation, migration and invasion of NPC cells by negatively regulating the expression of KLF7. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly and is the most common type of dementia. AD is mostly gradual onset, and involves slow, progressive mental decline, accompanied by personality changes; the incidence of AD gradually increases with age. The etiology of AD is unknown, although it is currently believed to be related to abnormal deposition of amyloid β-protein (Aβ) in the brain, hyperphosphorylation of microtubule-associated protein tau, and the release of various cytokines, complements, activators and chemokines by cells. MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs that regulate gene expression at the post-transcriptional level, and manipulate the functions of intracellular proteins and physiological processes. Emerging studies have shown that miRNA plays an important role in regulating AD-related genes. MiR-132 is known as "NeurimmiR" due to its involvement in numerous neurophysiological and pathological processes. Accumulating pre-clinical results suggest that miR-132 may be involved in the progression of Aβ and tau pathology. Moreover, clinical studies have indicated that decreased circulating miR-132 levels could be used a potential diagnostic biomarker in AD. Here, we review the pathogenic role of miR-132 activity in AD, and the potential of targeting miR-132 for developing future therapeutic strategies. [ABSTRACT FROM AUTHOR]

MicroRNAs play an important role in the modulation of the immune system. T helper 17 (Th17) cells are involved in the modulation of the tumour microenvironment. However, the function of miRNA in Th17 cells in the tumour microenvironment is unclear. In this study, we analysed miR‐132 expression in Th17 cells and assessed the function of miR‐132 on Th17 cell differentiation. In addition, the effect of miR‐132 on Th17 cells in the tumour microenvironment, especially hepatic stellate cells (HSCs), was confirmed. CD4+ IL‐17 ∓ cells were isolated from hepatocellular carcinoma (HCC) tumour tissues. The expression of miR‐132 was higher in CD4+ IL‐17 + cells than in CD4+ IL‐17‐ cells. Human primary CD4+ T cells were used for Th17 cell differentiation. Compared with primary CD4+ T cells, Th17 cells expressed high levels of miR‐132. During Th17 cell differentiation, a miR‐132 mimic and inhibition were applied. After treatment with the miR‐132 mimic, the differentiation of Th17 cells accelerated, showing a a higher percentage of Th17 cells and the expression and secretion of IL‐17 and IL‐22. Smad nuclear interacting protein 1 (SNIP1), as one of the targets of miR‐132, decreased during Th17 cell differentiation–related Th17 differentiation and IL‐17 expression. The conditioned medium of miR‐132–overexpressing Th17 cells could increase the activation of the HSCs, which strongly promoted HCC cell migration and epithelial‐mesenchymal transition (EMT). In summary, miR‐132 positively regulates Th17 cell differentiation and improves the function of Th17 on HSCs for their tumour‐promoting effects. [ABSTRACT FROM AUTHOR]

Aryl hydrocarbon receptor (AhR), is a transcription factor and an environmental sensor that has been shown to regulate T cell differentiation. Interestingly, AhR ligands exert varying effects from suppression to exacerbation of inflammation through induction of Tregs and Th-17 cells, respectively. In the current study, we investigated whether the differential effects of AhR ligands on T cell differentiation are mediated by miRNA during delayed-type hypersensitivity (DTH) reaction against methylated Bovine Serum Albumin (mBSA). Treatment of C57BL/6 mice with TCDD attenuated mBSA-mediated DTH response, induced Tregs, decreased Th-17 cells, and caused upregulation of miRNA-132. TCDD caused an increase in several Treg subsets including inducible peripheral, natural thymic, and Th3 cells. Also, TCDD increased TGF-β and Foxp3 expression. In contrast, treating mice with FICZ exacerbated the DTH response, induced inflammatory Th17 cells, induced IL-17, and RORγ. Analysis of miRNA profiles from draining lymph nodes showed that miR-132 was upregulated in the TCDD group and downregulated in the FICZ group. Transfection studies revealed that miRNA-132 targeted High Mobility Group Box 1 (HMGB1). Downregulation of HMGB1 caused an increase in FoxP3+ Treg differentiation and suppression of Th-17 cells while upregulation of HMGB1 caused opposite effects. Moreover, TCDD was less effective in suppressing DTH response and induction of Tregs in mice that were deficient in miR-132. In summary, this study demonstrates that TCDD and FICZ have divergent effects on DTH response and T cell differentiation, which is mediated through, at least in part, regulation of miRNA-132 that targets HMGB1.

Background: Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the functions of miRNA-132 (miR-132) in the modulation of PTEN/PI3K/AKT signaling pathway in the development and progression of osteoarthritis.Methods: Eight male osteoarthritic patients and eight healthy males were recruited. Male Sprague Dawley (SD) rats were used for cellular experiments. QRT-PCR was performed to detect the expression levels of miR-132, PTEN, PI3K and AKT. MTT assay and apoptosis assay were carried out to measure the cell proliferation rate and cell apoptosis rate, respectively. Western blotting was employed to detect the protein expression of related RNAs and inflammatory factors.Results: In osteoarthritic patients, the expression level of miR-132 was decreased, compared with that in the normal group. Over-expression of miR-132 elevated cell proliferation and decreased apoptosis of chondrocytes. Down-regulation of miR-132 decreased cell proliferation and induced apoptosis in chondrocytes. In addition, down-regulation of miR-132 promoted the expression of Bax protein and activated caspase-3/9, increased inflammation divisors. PTEN inhibitor antagonized the destructive effect of the miR-132 inhibitor on cell proliferation of chondrocytes. PI3K inhibitor increased the destructive effect of the miR-132 inhibitor on osteoarthritis.Conclusion: In conclusion, miR-132 is an important regulator of osteoarthritis in chondrocytes through the PTEN/PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune, multifactorial, inflammatory disorder characterized by hyperplasia and infiltration of inflammatory cells at the synovial lining leading to destruction of cartilage and bone tissues. Pinocembrin (PCB) is a natural flavonoid extracted as a pure molecule from honey, propolis, and some plants. In this study, we evaluated the antiarthritic effect of PCB in adjuvant induced arthritis (AIA) mice. Treating the AIA mouse model with PCB reduced the arthritis symptoms/score, including edema size, extent of hind paw redness, abnormal movement, and holding inability. At the pathological level, PCB significantly decreased the joint erosion and percentages of infiltrated inflammatory cells. Biochemically, PCB interacts with the transcription factor, SRY-related HMG-box 4 (Sox4), and then modulates its dysregulated expression and the expression of Sox4/Stat3 signaling molecules in AIA mice. These molecules include tumor necrosis factor-α, nuclear transcription factor kappaB, and cyclooxygenase-2, besides the microRNAs; miR-132, miR-202-5p, and miR-7235, which are dysregulated in adjuvant-induced arthritis model relative to the control mice. The possible PCB interaction with Sox4 transcriptional protein was confirmed through molecular docking where three hydrogen bonds were formed at ARG and LYS residues at a stable binding energy of −4.72. Taken together, our data demonstrate that PCB could serve as a therapeutic drug in treatment of RA. [ABSTRACT FROM AUTHOR]

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) has been verified as a crucial regulator in many types of tumours but not clear in cervical cancer (CC). This study aims to investigate the effect and further mechanisms of lncRNA SNHG5 in CC. The expression of SNHG5 and miR-132, as well as SOX4 (sex-determining region Y-box 4) mRNA expression were determined by quantitative real-time PCR (qRT-PCR). The protein level of SOX4 and epithelial-mesenchymal transition (EMT)-related proteins were evaluated by western blot. Then, Edu and Transwell assay were performed to assess the proliferation, migration and invasion of CC cells. RNA immunoprecipitation (RIP) and RNA pull-down assay were conducted to explore the relationship between SNHG5 and miR-132. SNHG5 and SOX4 were upregulated, and miR-132 was downregulated in CC tissues and cell lines. SNHG5 was positively correlated with FIGO stage (p =.003) and lymph node metastasis (p =.001). Pearson's correlation analysis conveyed that SNHG5 was positively correlated with SOX4, and miR-132 was negatively correlated with SOX4 and SNHG5. Knockdown of SNHG5 in vitro reduced CC cell proliferation, migration and invasion through regulating miR-132. Moreover, overexpression of miR-132 restrained CC cell proliferation, migration, and invasion through targeting SOX4, and SNHG5 enhanced SOX4 expression via negatively regulating miR-132. SNHG5 promotes SOX4 expression to accelerate CC cell proliferation, migration and invasion through negatively regulating miR-132. [ABSTRACT FROM AUTHOR]

Aryl hydrocarbon receptor (AhR), is a transcription factor and an environmental sensor that has been shown to regulate T cell differentiation. Interestingly, AhR ligands exert varying effects from suppression to exacerbation of inflammation through induction of Tregs and Th-17 cells, respectively. In the current study, we investigated whether the differential effects of AhR ligands on T cell differentiation are mediated by miRNA during delayed-type hypersensitivity (DTH) reaction against methylated Bovine Serum Albumin (mBSA). Treatment of C57BL/6 mice with TCDD attenuated mBSA-mediated DTH response, induced Tregs, decreased Th-17 cells, and caused upregulation of miRNA-132. TCDD caused an increase in several Treg subsets including inducible peripheral, natural thymic, and Th3 cells. Also, TCDD increased TGF-β and Foxp3 expression. In contrast, treating mice with FICZ exacerbated the DTH response, induced inflammatory Th17 cells, induced IL-17, and RORγ. Analysis of miRNA profiles from draining lymph nodes showed that miR-132 was upregulated in the TCDD group and downregulated in the FICZ group. Transfection studies revealed that miRNA-132 targeted High Mobility Group Box 1 (HMGB1). Downregulation of HMGB1 caused an increase in FoxP3+ Treg differentiation and suppression of Th-17 cells while upregulation of HMGB1 caused opposite effects. Moreover, TCDD was less effective in suppressing DTH response and induction of Tregs in mice that were deficient in miR-132. In summary, this study demonstrates that TCDD and FICZ have divergent effects on DTH response and T cell differentiation, which is mediated through, at least in part, regulation of miRNA-132 that targets HMGB1. [ABSTRACT FROM AUTHOR]

Fragile X-related protein 1 (FXR1) is a member of the fragile X family of RNA-binding proteins, which regulates a number of neurological and neuropsychiatric disorders such as fragile X syndrome, and is expected as a novel therapeutic target for some psychiatric diseases. However, it is unknown how FXR1 changes and functions in post-traumatic stress disorder (PTSD), a common mental disorder related to trauma and stressor. In this study, we characterized the expression pattern of FXR1 in the pathophysiological process of PTSD and further investigated the possible mechanism underlying these changes by finding an upstream regulator, namely miRNA-132 (miR-132). Furthermore, we verified whether miR-132 silence had an effect on the PTSD-like behaviors of single prolonged stress (SPS) rats through open field test, forced swimming test, and water maze test. At last, we examined the expression levels of PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We showed that the levels of FXR1 and fragile X mental retardation protein (FMRP), an autosomal homolog of FXR1, were decreased in the hippocampus of PTSD rats, but the levels of PSD95 and synapsin I were increased, which could be reversed by downregulation of miR-132. The results revealed that miR-132 could modulate PTSD-like behaviors in rats following SPS through regulating FXR1 and FMRP. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that act as key regulators in various physiological and pathological processes as prostate cancer (PCa). In this study we describe molecular evaluation of 132 and 212 miRNAs expression, by Real-time reverse-transcription PCR (qRT-PCR), in a Caucasian man 64-year-old with locally advanced PCa (PSA 160 ng/ml, Gleason score 4+3/ISUP Grade Group 3, clinical stage T3NXM0) who underwent radical retropubic prostatectomy plus extended pelvic lymphadenectomy (LAD) as first step of a multimodal therapeutic treatment. A normal prostate of a 67-year-old man removed by post mortem autopsy was used as a control in the study. The mRNA for this study was conducted on paraffined prostatic sections of: a) index case of PCa; b) metastatic lymph node of index case; c) normal prostate. MiRNA-132, miRNA- 212 and Glyceraldehyde 3-phosphate dehydrogenase (as reference gene) assays were obtained. Definitive specimen showed a pT3bN1R1 stage: acinar cells adenocarcinoma with involvement of the seminal vesicles, multifocal positive surgical margins, Gleason score 8 (4+4/ISUP Grade Group 4), metastases in 5/25 iliac lymph nodes. An increased expression of miRNA-132 and miRNA-212 in index case of prostatic adenocarcinoma compared to normal prostate tissue was found; moreover, a lower expression of miR-132 and miR-212 in metastatic lymph node compared to primitive PCa and normal prostate tissue was demonstrated. Although a greater number of patients should be evaluated, these data suggest that the biology of the primary PCa, in our clinical case, was different from metastatic lymph node.