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目的 探讨葡萄膜黑色素瘤（UM）组织微小RNA（miR-）144、miR-145表达变化及其与患者预后的关系。方法 选取140例（140眼）UM患者（观察组）、100例（100眼）因外伤行眼球摘除术的患者（对照组). 取两组手术切除的葡萄膜组织, 采用real-time PCR法检测miR-144、miR-145。比较两组miR-144、miR-145表达情况, 以均数为界值将UM患者分为miR-144低表达、高表达以及miR-145低表达、高表达者, 比较不同临床病理特征UM患者miR-144、miR-145高表达和低表达情况, 采用Kaplan-Meier分析比较miR-144、miR-145高表达和低表达患者的预后, COX回归模型分析UM预后的影响因素。结果 观察组病变组织miR-144、miR-145表达低于对照组（P均＜0.05). 观察组miR-144低表达69例、高表达71例, miR-145低表达73例、高表达67例。与无虹膜新生血管、肿瘤厚度≤8 mm、无眼外生长、T分期T1～T2期的UM患者比较, 有虹膜新生血管、肿瘤厚度＞8 mm、有眼外生长、T分期T3～T4的UM患者miR-144、miR-145低表达者占比增加, miR-144、miR-145高表达者占比减少（P均＜0.05). miR-144、miR-145低表达UM患者5年生存率低于miR-144、miR-145高表达患者（P均＜0.01). 肿瘤厚度＞8 mm及miR-144、miR-145低表达是UA患者预后不良的独立危险因素（P均＜0.05). 结论 UM组织中miR-144、miR-145表达降低, miR-144、miR-145低表达与UM患者不良预后有关. [ABSTRACT FROM AUTHOR]

Abstract Background Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB). Methods Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively. Results After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%. Conclusion miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum. Systematic review registration PROSPERO (CRD42022302729).

Background: Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB). Methods: Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively. Results: After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%. Conclusion: miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum. Systematic review registration: PROSPERO (CRD42022302729). [ABSTRACT FROM AUTHOR]

Although the previous research confirmed that triclosan (TCS) induced an estrogen effect by acting on a novel G-protein coupled estrogen-membrane receptor (GPER), the underlying mechanisms by which downstream pathways induce neurotoxicity remain unclear after TCS activation of GPER. By employing a series of techniques (Illumina miRNA-seq, RT-qPCR, and artificial intervention of miRNA expression), we screened out four important miRNAs, whose target genes were directly/indirectly involved in neurodevelopment and neurobehavior. Especially, the miR-144 up-regulation caused vascular malformation and severely affected hair-cell development and lateral-line-neuromast formation, thereby causing abnormal motor behavior. After microinjecting 1-2-cell embryos, the similar phenotypic malformations as those induced by TCS were observed, including aberrant neuromast, cuticular-plate development and motor behavior. By KEGG pathway enrichment analysis, these target genes were demonstrated to be mainly related to the PKC/MAPK signaling pathway. When a PKC inhibitor was used to suppress the PKC/MAPK pathway, a substantial alleviation of TCS-induced neurotoxicity was observed. Therefore, TCS acts on GPER to activate the downstream PKC/MAPK signaling pathway, further up-regulating miR-144 expression and causing abnormal modulation of these nerve-related genes to trigger neurodevelopmental toxicity. These findings unravel the molecular mechanisms of TCS-induced neurodegenerative diseases, and offer theoretical guidance for TCS-pollution early warning and management.

Objective To investigate the effect of total flavonoids of Hippophae rhamnoides L.(HTF) on the proliferation and apoptosis of bladder cancer cell line T24 and underlying mechanism. Methods The bladder cancer T24 cells were incubated with different concentrations (25, 50, 100 μg/mL) of HTF for 24 h, then CCK-8 assay, flow cytometry and Western blot were used to detect proliferation, apoptosis and the expression of Bcl-2 and Bax proteins, respectively. The expression of miR-144 was detected by RT-qPCR. miR-144 inhibitors were transfected into T24 cells to construct T24 cells whose expression of miR-144 was knocked down,then 100 μg/mL HTF was used to interfere with the miR-144-knoched down T24 cells. The same methods were used to detect the effects of knocking down of miR-144 on cell proliferation and apoptosis of T24 cell. Results Compared with the control group, different concentrations of HTF reduced the cell A value and the expression of Bcl-2, and increased the apoptosis rate and the expression of Bax. At the same time, the expression of miR-144 (P

Background: Preeclampsia (PE) is a common and severe hypertensive disorder in pregnancy. Mesenchymal stem cell-derived exosomes (Exos-MSC) have been reported to mitigate the progression of inflammatory diseases. The study aimed to explore the effects of human umbilical cord-derived Exos-MSC (huc-Exos-MSC) on PE-like models. Methods: Lipopolysaccharide (LPS) was used to construct in vitro and in vivo PE-like models. Exosomes were treated with LPS-induced PE-like cells and rats. Results: PE-like inflammatory models of pregnant rats and cells were successfully constructed in vivo and in vitro. miR-144 was screened by bioinformatics analysis. Exosomes were successfully extracted. Silencing FosB, overexpressing miR-144 or treating with exosomes extracted from huc-MSC overexpressing miR-144 in (Exos-MSCmiR−144) reversed the LPS-induced decline in HTR-8/SVneo cell viability and migration. In addition, the above groups decreased LPS-induced increases in interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), phosphorylated nuclear factor-kappaB (p–NF–κB)/NF-κB, soluble FMS-like tyrosine kinase 1 (sFlt-1), and Flt-1 levels. Simultaneously, transfection of miR-144 mimics and overexpressing FosB reversed those changes in the miR-144 mimics group. miR-144 might alleviate LPS-induced HTR-8/SVneo cell inflammation by targeting FosB. Injection of Exos-MSCmiR−144 in PE-like pregnant rats reversed LPS-induced increases in FosB expression, systolic and diastolic blood pressure (SBP and DBP), as well as mean arterial pressure (MAP), heart rate, urine albumin/creatine ratio, inflammatory factors, p–NF–κB/NF-κB, and sFlt-1 levels. Furthermore, compared with the model group, the proportion of live births was significantly higher in the model + Exos-MSCmiR−144 group, while the apoptosis rate of fetal rat brain tissue was significantly lower. Conclusions: We found that huc-Exos-MSC-derived miR-144 alleviated gestational hypertension and inflammation in PE-like pregnant rats by regulating the FosB/Flt-1 pathway. In addition, huc-Exos-MSC-derived miR-144 could partially reverse the LPS-induced adverse pregnancy outcome and brain injury in fetal rats, laying the foundation for developing new treatments for PE.

Abstract Nonsmall cell lung cancer (NSCLC) is a major subtype of lung cancer, causing substantial cancer‐related deaths worldwide. However, the molecular basis of NSCLC development and progression remains understudied. Recently, a circular RNA, circDLG1, has been implicated in carcinogenesis and cancer metastasis. Yet, how circDLG1 affects NSCLC progression has not been reported. Here this study aims to elucidate the role of circDLG1 in NSCLC. First, we found that circDLG1 was significantly upregulated in both the GEO dataset and NSCLC tissues. Next, we silenced the expression of circDLG1 in NSCLC cell lines. Knockdown of circDLG1 upregulated miR‐144 and downregulated Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), resulting in suppression of the proliferation activity and metastasis ability of NSCLC. In addition, circDLG1 knockdown significantly decreased the expression of the mesenchymal markers, proliferating cell nuclear antigen (PCNA), and N‐cadherin, while increasing the expression level of E‐cadherin. In conclusion, we demonstrate that circDLG1 promotes the pathogenesis and progression of NSCLC by regulating the miR‐144/AKT/mTOR signaling axis, providing potential diagnostic and therapeutic targets for designing innovative treatment strategies.

Background: Hirschsprung's disease (HSCR) is characterized by a dysfunction of enteric neural crest cells (ENCCs) proliferation, migration and premature apoptosis during embryonic development, resulting in aganglionic colon. Our aim is to explore the role of miR-144 with its target gene Transcription Factor AP 4 (TFAP4) in nerve cells in HSCR. Methods: The relative expression levels of miR-144 in HSCR colon samples were detected by quantitative real-time PCR (RT-qPCR). Western blot assays were conducted to investigate the TFAP4 protein expressing level. The interaction of miR-144 and TFAP4 was predicted with bioinformatics analysis and examined with luciferase reporter assays. Overexpression or knockdown of miR-144 and TFAP4 in 293T and SH-SY5Y cell lines was applied. Cell proliferation, migration and invasion were detected by CCK-8 assays, Transwell migration and invasion assays. Cell cycle and apoptosis was examined by flow cytometric analysis. Results: Downregulation of miR-144 and upregulation of TFAP4 were shown in HSCR. Luciferase reporter assay indicated that miR-144 reduced luciferase activity in 293T and SH-SY5Y transfected with TFAP4-WT-3UTR luciferase reporter and confirmed TFAP4 was the downstream target gene of miR-144. Data showed that miR-144 promoted the cell proliferation, migration and invasion of 293T and SH-SY5Y, while TFAP4 blocked the cell proliferation, migration and invasion. TFAP4 overexpression reversed the miR-144-mediated cell proliferation, migration and invasion of 293T and SH-SY5Y. Conclusions: Downregulation of miR-144 blocked the cell proliferation and migration of nerve cells via targeting TFAP4 and contributed to the pathogenesis of HSCR. This provides an innovative and candidate target for treatment of HSCR. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of total flavonoids of Hippophae rhamnoides L.(HTF) on the proliferation and apoptosis of bladder cancer cell line T24 and underlying mechanism. Methods The bladder cancer T24 cells were incubated with different concentrations (25, 50, 100 μg/mL) of HTF for 24 h, then CCK-8 assay, flow cytometry and Western blot were used to detect proliferation, apoptosis and the expression of Bcl-2 and Bax proteins, respectively. The expression of miR-144 was detected by RT-qPCR. miR-144 inhibitors were transfected into T24 cells to construct T24 cells whose expression of miR-144 was knocked down,then 100 μg/mL HTF was used to interfere with the miR-144-knoched down T24 cells. The same methods were used to detect the effects of knocking down of miR-144 on cell proliferation and apoptosis of T24 cell. Results Compared with the control group, different concentrations of HTF reduced the cell A value and the expression of Bcl-2, and increased the apoptosis rate and the expression of Bax. At the same time, the expression of miR-144 (P<0.05) was increased.The A value of T24 cells that knocked down miR-144 and the expression of Bcl-2 protein in the cells was higher than those of control T24 cells(P<0.05), but the apoptosis rate and the expression of Bax protein were lower(P<0.05). After T24 cells that knocked down miR-144 were treated with 100 μg/mL HTF, their A value and the expression of Bcl-2 protein in the cells were higher than those of T24 cells that not knocked down miR-144(P<0.05), but the apoptosis rate and the expression of Bax protein were lower than those of control T24 cells (P<0.05). Conclusions HTF may slow-down the proliferation of bladder cancer cells and speed-up their apoptosis by up-regulating miR-144. [ABSTRACT FROM AUTHOR]

Background Intimal hyperplasia contributed by phenotypic switching of vascular smooth muscle cell (VSMC) plays an important role in the pathogenesis of various cardiovascular diseases. MicroRNA-144 (miR-144) is recently reported to be implicated in the development of atherosclerosis. However, the individual role of miR-144 in VSMCs phenotypic modulation and intimal hyperplasia currently still remains unknown. Methods and Results Here we found that miR-144 expression was upregulated in carotid arteries with intimal hyperplasia that subjected to wire injury and the consistent results were obtained with dedifferentiated VSMCs upon platelet-derived growth factor-BB (PDGF-BB) stimulation. Loss-of-function study showed that miR-144 knockdown decreased the ability of VSMC proliferation tested by Brdu and CCK8, and reduced the migrate capability analyzed by Transwell, whereas increased the differentiated SMC marker gene expression examined by RT-PCR. The above results were reversed by miR-144 overexpression. Mechanistically, we have demonstrated that PTEN was the direct target of miR-144 that was responsible for the alleviated effect of miR-144 inhibition on phenotypic switching of VSMCs. Notably, mice injected with miR-144 inhibitor attenuated the formation of neointimal lesions in response to wire injury and maintained the mature SMC marker expression inhibited the proliferation and migration of VSMCs. Conclusion Our research exhibited that miR-144 knockdown attenuated intimal hyperplasia through inhibiting the VSMC phenotypic switching, which was partially mediated by directly targeting to PTEN. Taken together, these evidences suggested that miR-144 may act as a promising therapeutic target for arterial restenosis.

Nonsmall cell lung cancer (NSCLC) is a major subtype of lung cancer, causing substantial cancer‐related deaths worldwide. However, the molecular basis of NSCLC development and progression remains understudied. Recently, a circular RNA, circDLG1, has been implicated in carcinogenesis and cancer metastasis. Yet, how circDLG1 affects NSCLC progression has not been reported. Here this study aims to elucidate the role of circDLG1 in NSCLC. First, we found that circDLG1 was significantly upregulated in both the GEO dataset and NSCLC tissues. Next, we silenced the expression of circDLG1 in NSCLC cell lines. Knockdown of circDLG1 upregulated miR‐144 and downregulated Protein kinase B (AKT)/mechanistic target of rapamycin (mTOR), resulting in suppression of the proliferation activity and metastasis ability of NSCLC. In addition, circDLG1 knockdown significantly decreased the expression of the mesenchymal markers, proliferating cell nuclear antigen (PCNA), and N‐cadherin, while increasing the expression level of E‐cadherin. In conclusion, we demonstrate that circDLG1 promotes the pathogenesis and progression of NSCLC by regulating the miR‐144/AKT/mTOR signaling axis, providing potential diagnostic and therapeutic targets for designing innovative treatment strategies. [ABSTRACT FROM AUTHOR]

Objectives: MicroRNA (miRNA) clusters co‐transcribe and function in a coordinated fashion mediating synergistic or antagonistic regulatory effects. MiR‐144 and miR‐451a are deregulated in various cancers but the combined regulatory role of miR‐144/451a cluster in oral squamous cell carcinoma (OSCC) remains unexplored. In the present study, we studied the synergistic effect of miR‐144/451a cluster on oral cancer progression. Materials and methods: miR‐144 and miR‐451a expression was explored in OSCC cell lines by quantitative real‐time PCR (qRT‐PCR). Proliferation, wound healing, migration and invasion, spheroid formation, and colony formation assays were performed after transfection with miR‐144‐3p, miR‐451a, miR‐144‐5p, and co‐expressed miR‐144/451a. Expression of putative target genes was analyzed using qRT‐PCR and Western blotting. Results: miR‐144 and miR‐451a were downregulated in all cell lines. The cell viability and stemness of cancer cell lines were unaltered when treated with miRNA mimics. However, co‐expressed miR‐144/451a significantly reduced the migratory, invasive, and clonogenic potential of cells than individual miRNAs. Conclusion: miR‐144/451a cluster functions as a tumor suppressor in OSCC by inhibiting cancer cell invasion, migration, and clonogenic potential. [ABSTRACT FROM AUTHOR]

IUR is a recently identified oncogenic lncRNA in leukaemia, while its roles in nasopharyngeal carcinoma (NPC) are unclear. We aimed to explore the possible involvement of IUR in NPC. IUR and PTEN were downregulated, while miR-144 was upregulated in NPC. In addition, IUR was inversely correlated with miR-144 and positively correlated with PTEN. In NPC cells, overexpression of IUR resulted in a downregulated expression of miR-144 and an upregulated expression of PTEN. Overexpression of miR-144 led to a downregulated expression of PTEN and attenuated the effects of overexpression of IUR. Cell proliferation assay showed that overexpression of IUR and PTEN resulted in decreased NPC cell proliferation rate. Overexpression of miR-144 played an opposite role and attenuated the effects of overexpression of IUR. In conclusion, IUR can downregulate miR-144 to upregulate PTEN in NPC, therefore inhibiting NPC cell proliferation. [ABSTRACT FROM AUTHOR]

Context: In vitro maturation (IVM) of oocytes is an alternative approach for patients with polycystic ovary syndrome (PCOS) predisposing to ovarian hyperstimulation syndrome (OHSS). Transcriptomic analysis of cumulus cells (CC) may help make IVM more efficient. The aim of this study was to examine the impact of miR-144 and miR-224 and their candidate target genes (COX-2 and PTX-3 , respectively) expression on oocyte development in PCOS patients. Methods: Immature oocytes were retrieved from 20 PCOS patients. After IVM, samples were divided into two groups: matured (M) and immatured (I) oocytes. ICSI was performed and the embryo quality was evaluated. qPCR was used to analyse miR-144, miR-224, COX-2 and PTX-3 expression levels in CCs of each group. Key results: We found that the expression levels of miR-144 and miR-224 were lower and the COX-2 and PTX-3 mRNA levels were higher in CCs of M group than in CCs of I group. The expression level of miR-144 and miR-224 in unfertilised oocytes were higher than fertilised oocytes. The contrary results were observed for COX-2 and PTX-3. A reduction pattern in the expression level of miR-144 and miR-224 and increasing pattern in the level of COX-2 and PTX-3 expression were observed in high quality compared to low quality embryos. Conclusions: The selected miRNAs were related to oocyte maturation, fertilisation and embryo development. These results support their critical involvement in oocyte development. Implications: Our findings may help reveal the mechanisms of post-transcriptional regulation by miR-144 and miR-224 during IVM procedure. The expression level of miR-144 and miR-224 in cumulus cells of patients with polycystic ovary syndrome may be related to oocyte development. They can affect oocyte in vitro maturation (IVM) and fertilisation outcome by regulating their target genes (COX-2 and PTX-3 , respectively). So, we suggested that the selected miRNAs may help to make IVM more efficient. [ABSTRACT FROM AUTHOR]

Intimal hyperplasia contributed by phenotypic switching of vascular smooth muscle cell (VSMC) plays an important role in the pathogenesis of various cardiovascular diseases. MicroRNA-144 (miR-144) is recently reported to be implicated in the development of atherosclerosis. However, the individual role of miR-144 in VSMCs phenotypic modulation and intimal hyperplasia currently still remains unknown. Here we found that miR-144 expression was upregulated in carotid arteries with intimal hyperplasia that subjected to wire injury and the consistent results were obtained with dedifferentiated VSMCs upon platelet-derived growth factor-BB (PDGF-BB) stimulation. Loss-of-function study showed that miR-144 knockdown decreased the ability of VSMC proliferation tested by Brdu and CCK8, and reduced the migrate capability analyzed by Transwell, whereas increased the differentiated SMC marker gene expression examined by RT-PCR. The above results were reversed by miR-144 overexpression. Mechanistically, we have demonstrated that PTEN was the direct target of miR-144 that was responsible for the alleviated effect of miR-144 inhibition on phenotypic switching of VSMCs. Notably, mice injected with miR-144 inhibitor attenuated the formation of neointimal lesions in response to wire injury and maintained the mature SMC marker expression inhibited the proliferation and migration of VSMCs. Our research exhibited that miR-144 knockdown attenuated intimal hyperplasia through inhibiting the VSMC phenotypic switching, which was partially mediated by directly targeting to PTEN. Taken together, these evidences suggested that miR-144 may act as a promising therapeutic target for arterial restenosis. [ABSTRACT FROM AUTHOR]

Despite the extensive therapeutic uses of diclofenac, it may cause several adverse effects, including hepatorenal injury. The antioxidant and anti‐inflammatory properties of resveratrol, a polyphenolic compound, make the agent effective in ameliorating a variety of drug‐induced injuries. This study investigated the potential beneficial effects of resveratrol on diclofenac‐induced hepatorenal toxicity and explored the role of miR‐144 and its relationship to oxidative stress and inflammation triggered by diclofenac. Rats were divided into four groups: control; diclofenac group received diclofenac (10 mg/kg/day, intraperitoneal [ip]) for 7 days; prevention group received resveratrol concomitantly with diclofenac for 7 days; and the treatment group received diclofenac for 7 days followed by resveratrol (20 mg/kg/day, per oral) for another 7 days. Diclofenac administration induced a significant increase in serum hepatorenal biomarkers and histopathological aberrations. In addition, diclofenac upregulated miR‐144 while reducing nuclear factor erythroid 2‐related factor 2 (Nrf2) protein levels and glutathione (GSH) content. Moreover, diclofenac induced tissue inflammation and apoptosis as evidenced by increased protein expression of nuclear factor kappa B (NF‐κB), tumor necrosis factor α (TNF‐α), and caspase‐3. Intriguingly, resveratrol prevention or treatment significantly mitigated the toxic effects of diclofenac as manifested by normalization of the hepatorenal functions and amelioration of the histopathological changes. Resveratrol also triggered miR‐144 downregulation with Nrf2 upregulation. Consequently, resveratrol showed hepatorenal antioxidant, anti‐inflammatory, and antiapoptotic activities as manifested by improvement in the antioxidant markers along with a decline in NF‐κB, TNF‐α, and caspase‐3 expressions. In conclusion, this study demonstrates a potential therapeutic role of resveratrol in mitigating diclofenac‐induced hepatorenal insult, possibly via modulating miR‐144/Nrf2/GSH axis. Highlights: miR‐144 is implicated in diclofenac‐evoked hepatorenal insults.Resveratrol cotreatment or treatment mitigates the toxic effects of diclofenac.Resveratrol protects from diclofenac toxicity via modulating miR‐144/Nrf2/GSH axis [ABSTRACT FROM AUTHOR]

Objective: To explore the effects of berberine on A549 lung cancer cells and corresponding changes in miR-144 expression, and the apoptosis and autophagy pathways. Methods: Cell proliferation was detected by cell counting Kit-8. The expression of miR-144 by quantitative PCR, caspase-3, caspase-3 cleaved, Bcl-2, Bax, beclin-1, LC3I, and LC3II were assessed using Western blot. Results: A549 proliferation was reduced with increasing berberine concentration. Berberine appeared to suppress A549 proliferation through apoptosis and autophagy, and, additionally, enhanced miR-144 expression. Berberine promoted A549 cell apoptosis by inhibiting caspase-3 cleavage and Bcl-2 expression and promoting Bax expression. Berberine also promoted A549 autophagy by raising the expression of beclin-1, LC3I, and LC3II. Conclusions: Berberine promotes A549 apoptosis and autophagy via miR-144. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) which are small non-coding RNAs have been reported to be potential cancer biomarker. However, it is difficult to extract such short RNA from a sample matrix. New effective strategies are required. Recently, graphene quantum dots (GQDs) have been used to detect nucleotides in many biosensor platforms, but their applications for miRNA extraction remain limited. GQD was reported to be able to collect short miRNA, but its performance to collect miRNAs with different structure remains unknown. Thus, in this work, the capability of GQD to interact with two different miRNAs is investigated. A mixture of hairpin-like miR-29a and circular miR-144 molecules are used as a representative of two miRNA morphologies. Two systems (a miRNA mixture, comprising 4 of miR-29a and 4 of miR-144, with (miR&#95;GQD) and without GQD (miR)) were studied in comparison. MiRNAs in a mixture (miR) can aggregate, but no permanent miRNA assembly is captured. In contrast, the presence of GQD can rapidly and spontaneously activate the permanent miRNA/GQD clustering. This finding highlights the ability of GQD to be a miRNA collector. Interestingly, all GQD-bound miRNAs do not unfold. This allows the easy accessibility for probes. Also, nano-sized GQD seems to prefer hairpin miR-29a. The free 5' terminus of miR-29a acts as the sticky end to adhere on GQD. This work highlights the importance of RNA secondary structure on GQD/miRNA aggregation capability. An insight obtained here will be useful for further design of miRNA isolation strategies., Competing Interests: Declaration of competing interest This manuscript is original, has not been published before and is not currently being considered for publication elsewhere. There are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024. Published by Elsevier Inc.)

MicroRNAs (miRNAs) are short noncoding sequences that can regulate the expression of target genes. Erythrocytes, also called red blood cells (RBCs), are the largest proportion of cells in blood. Erythrocytes deliver oxygen in the body of vertebrates and contribute to the body's immune function. Illumina sequencing technology was used to analyze pooled RNA samples isolated from erythrocytes, in order to characterize their gene expression profile and increase the range of miRNAs identified in Nile tilapia erythrocytes. This study identified conserved (n = 309) and novel (n = 194) miRNAs. Quantitative reverse-transcription polymerase chain reaction and next-generation sequencing results indicated that miR-451 was the most abundant in RBCs, followed by let-7a-1, miR-2188 and miR-144. Moreover, the tissue expression mode of these highly expressed miRNAs was characterized. Results show that miR-451, miR-2188, and miR-144 were all highly expressed in RBCs but were low abundance in other tissues. miR-1 and miR-10b were also abundantly expressed in muscle, while miR-122 was abundantly expressed in the liver. let-7a-1, miR-10b, and miR-1 were significantly higher in the testis than in the ovary. The tissue distribution of miRNAs implies that these noncoding sequences have a potential role in regulating tissue differentiation or maintaining tissue characteristics. The results of a dual-luciferase reporter assay indicated that miR-144 and miR-10b inhibited the expression of the meningioma expressed antigen 5 gene in vitro. This study contributes to the Nile tilapia miRNA database and reveals the profile of erythrocyte miRNA expression.

UCP4, as an uncoupling protein in mitochondrial intima, is closely related to the resistance to oxidative stress and the function of mitochondria. However, whether and how its antioxidant capacity also works in crustaceans has not been reported in detail. This study showed that the expression of Pv UCP4 was negatively correlated with the expression of pva-miR-144. The content of reactive oxygen species (ROS), ATP, and apoptosis was significantly increased, while the mitochondrial membrane potential (MMP) was seriously depolarized, Edema, vacuolation, and ambiguity of cristae and membrane were observed clearly in mitochondria after the knockdown of Pv UCP4 induced by V. alginolyticus. The sharp drop in THC and severe damage in the hepatopancreas were all due to the knockout of PvUCP4 under the stress of V. alginolyticus. The co-transfection of pva-miR-144 and Pv UCP4 could partially recover MMP compared with the abnormal expression of pva-miR-144. Similarly, co-transfection of pva-miR-144 and Pv UCP4 could partially eliminate apoptosis compared with the abnormal expression of pva-miR-144. In addition, Pv UCP4 3′-UTR has a pva-miR-144 predicted binding site in 1417–1428, which also was confirmed by the dual luciferase reporter assay. By the way, the results of ROS, MMP, and apoptosis showed that Pv DJ-1 regulated the expression of PvUCP4 through Pv NF-κB. Altogether, these results indicated that PvUCP4 has the antioxidant function of resisting oxidation reaction and weakening oxidative damage, to protect the normal operation of mitochondrial function and maintaining the cell homeostasis in shrimp. • Pv UCP4responds to V. alginolyticus stress by maintain mitochondrial homeostasis. • Pva-miR-144 maintain mitochondrial homeostasis via targeting of Pv UCP4. • Pv DJ-1 regulated the expression of PvUCP4 through Pv NF-κB. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is a severe health condition characterized by high mortalities. NudC domain containing 1 (NUDCD1) is abnormally upregulated in multiple tumors and is recognized as a cancer antigen. In CRC, NUDCD1 upregulation accelerates tumor progression by activating the IGF1R-ERK1/2 signaling pathway. Its specific regulatory mechanisms, however, remain unclear. Methods: In the present study, we predicted the regulators of NUDCD1 and analyzed the expression profile of NUDCD1 in CRC tissues using the gene chip dataset. We also determined the regulation between miR-144, NUDCD1 and IGF1R-ERK1/2 signaling in vitro and in vivo. Then, the expression of miR-144 in CRC tissues was detected and its cell functions were verified in vitro. Results: As predicted by bioinformatics, we found that NUDCD1 is a predicted target of miR-144 and confirmed that miR-144 directly binds to NUDCD1. In vitro and in vivo, miR-144 was determined to specifically regulate NUDCD1 expression and as such, can reduce the activity of the IGF1R-ERK1/2 signaling pathway. Moreover, miR-144 was significantly downregulated in CRC tissues; its levels were significantly negatively correlated with CRC primary range and lymph node metastasis. Cell function studies verified that miR-144 acts as a tumor suppressor, because it significantly inhibits the proliferation, metastasis, and invasion of CRC cells as well as inducing cell cycle arrest and apoptosis. Conclusions: Our study demonstrates that miR-144 regulates IGF1R-ERK1/2 signaling via NUDCD1 to inhibit CRC cell proliferation and metastasis. The miR-144/NUDCD1/IGF1R-ERK1/2 signaling axis may be crucial in the progression of CRC. [ABSTRACT FROM AUTHOR]

CeRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, C/EBPα was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of C/EBPα and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of C/EBPα and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ , thereby influencing pre-adipocytes adipogenesis. More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of C/EBPα and FOXO1 to influence AdipoQ , thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis. • In this research, we first reported the miR-144 mediated the C/EBPα-FOXO1 complex formation by the ceRNA effect. • C/EBPα-FOXO1 protein complex was regulated by miR-144 thus infected its adipogenic role for AdipoQ. • This research was the first study to explore the interaction of the miRNA targeted coding genes by ceRNA effect. • Our report will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction, especially for the adipogenesis. [ABSTRACT FROM AUTHOR]

Chong Lu,1,* Yikui Zhao,2,* Yan Cao,3,* Li Liu,1 Shanshan Wu,1 Dongbin Li,1 Shuang Liu,1 Shuyuan Xiao,1 Yafen Wei,1 Xinyu Li3 1Department of Neurology, Heilongjiang Provincial Hospital, Harbin, People’s Republic of China; 2HIT Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, People’s Republic of China; 3Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinyu Li; Yafen Wei Tel +86-13796658016; Tel +86-13796658016Email 13796658016@163.com; weiyafen2008@sina.comAim: High glucose (HG)-induced activation of mTOR promotes tau phosphorylation and leads to diabetes-associated dementia. This study aimed to explore the role of metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) in HG-induced neuronal cell injury.Methods: Hippocampus cells were isolated from C57BL/6J mice. After 6 days of culture, the cells were incubated with 5.5 mM glucose in normal medium or 75 mM glucose for 4 days. Cells were transfected with miR-144 mimic, miR-144 inhibitor, siRNA for MALAT1 or corresponding controls. Gene expression was detected by PCR and Western blot analysis.Results: HG increased the levels of MALAT1 and p-tau in hippocampal cells. Knockdown of MALAT1 partially reversed the effects of HG on mTOR activity and p-tau protein levels. MALAT1 functioned as competing endogenous RNA (ceRNA) for miR-144, and pre-treatment with MALAT1 siRNA decreased mTOR activity and p-tau protein level in HG-treated hippocampal cells, which was significantly attenuated by miR-144 mimics. Moreover, miR-144 negatively regulated the expression of mTOR and knockdown of MALAT1 suppressed mTOR, while overexpression of mTOR abrogated protective effects of MALAT1 knockdown in HG-treated hippocampal cells.Conclusion: MALAT1 knockdown prevented HG-induced mTOR activation and inhibited tau phosphorylation. MALAT1 may be a therapy target for diabetes associated dementia.Keywords: diabetes mellitus, tau, MALAT1, mTOR, miR-144

Abstract Background & Aims Hepatocellular carcinoma (HCC) is among the malignancies with the highest mortality. The key regulators and their interactive network in HCC pathogenesis remain unclear. Along with genetic mutations, aberrant epigenetic paradigms, including deregulated microRNAs (miRNAs), exert profound impacts on hepatocyte transformation and tumor microenvironment remodeling; however, the underlying mechanisms are largely uncharacterized. Methods We performed RNA sequencing on HCC specimens and bioinformatic analyses to identify tumor-associated miRNAs. The miRNA functional targets and their effects on tumor-infiltrating immune cells were investigated. The upstream events, particularly the epigenetic mechanisms responsible for miRNA deregulation in HCC, were explored. Results The miR-144/miR-451a cluster was downregulated in HCC and predicted a better HCC patient prognosis. These miRNAs promoted macrophage M1 polarization and antitumor activity by targeting hepatocyte growth factor (HGF) and macrophage migration inhibitory factor (MIF). The miR-144/miR-451a cluster and EZH2, the catalytic subunit of polycomb repressive complex (PRC2), formed a feedback circuit in which miR-144 targeted EZH2 and PRC2 epigenetically repressed the miRNA genes via histone H3K27 methylation of the promoter. The miRNA cluster was coordinately silenced by distal enhancer hypermethylation, disrupting chromatin loop formation and enhancer-promoter interactions. Clinical examinations indicated that methylation of this chromatin region is a potential HCC biomarker. Conclusions Our study revealed novel mechanisms underlying miR-144/miR-451a cluster deregulation and the crosstalk between malignant cells and tumor-associated macrophages (TAMs) in HCC, providing new insights into HCC pathogenesis and diagnostic strategies.

MicroRNAs are increasingly recognized for their pivotal role in the immune system, yet the specific regulatory functions of fish-derived microRNAs remain largely unexplored. In this research, we discovered a novel miRNA, Cse-miR-144, in the Chinese tongue sole (Cynoglossus semilaevis), characterized by a 73-base pair precursor and a 21-nucleotide mature sequence. Our findings revealed that the expression of Cse-miR-144 was notably inhibited by various Vibrio species. Utilizing bioinformatics and dual-luciferase assay techniques, we established that the pro-inflammatory cytokine gene CsMAPK6 is a direct target of Cse-miR-144. Subsequent in vitro and in vivo western blotting analyses confirmed that Cse-miR-144 can effectively reduce the protein levels of CsMAPK6 post-transcriptionally. Moreover, CsMAPK6 is known to be involved in the activation of the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB). Additional investigations using qPCR and ELISA demonstrated that suppression of Cse-miR-144 leads to an upsurge in the liver mRNA levels of various immune genes (including MYD88 , TRAF6 , NF -κB , TRAF2 , TRAF3 , and TNF), alongside a marked increase in the production and secretion of pro-inflammatory cytokines (IL-1β, IL-6, and IL-8) in the bloodstream of C. semilaevis. These findings collectively underscore the potential of Cse-miR-144 as a key inhibitor of CsMAPK and its crucial role in modulating the immune and inflammatory responses in teleost fish. Compared to the siRNA, miRNA is a better tool in controlling the expression of target gene with a lower cost. • A novel Cse-miR-144 with potential regulatory impacts on the infection of Vibrio by targeting CsMAPK6 gene was analysis. • Cse-miR-144 has been shown effect on the production of pro-inflammatory cytokines in by downregulating CsMAPK6. • Cse-miR-144 are more efficient than siRNAs for expression control of CsMAPK6 gene and immune response modulation. [ABSTRACT FROM AUTHOR]

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Yuhuan Li,1 Nina Wang,2 Jie Pan,2 Xinrui Wang,1 Yanling Zhao,3 Zongjun Guo4 1Department of Psychology, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People’s Republic of China; 2Department of Pharmacy, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People’s Republic of China; 3Department of Methadone Clinic, Qingdao Mental Health Center, Qingdao City, Shandong Province, 266000, People’s Republic of China; 4Department of Geriatric Internal Medicine, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, 266000, People’s Republic of ChinaCorrespondence: Xinrui WangDepartment of Psychology, Qingdao Mental Health Center, No. 9 Dong ‘an Road, North District, Qingdao City, Shandong Province, 266000, People’s Republic of ChinaTel +86 532-8093158Email ffssmh256766237@126.comBackground: Depression is the common mental disorder in the world. However, the pathophysiology mechanism underlying depression remains elusive. It has been reported that aberrant expression of miR-144 is closely related to depression. This study was to investigate whether and how miR-144 involves in depressive-like behaviors in a chronic unpredictable mild stress (CUMS) animal model.Methods: A rat model of CUMS was established, and qRT-PCR was performed to detect the expression of miR-144 in the hippocampus of a depressed rat. The lentiviral vector carried miR-144 (LV-miR-144) was injected into the hippocampus of the CUMS rat to investigate the effects of miR-144 on the behaviors and PTP1B/TrkB/BDNF signal transduction in the hippocampus of the rat. The interaction between miR-144 and PTP1B was investigated by biological analyses and dual-luciferase reporter assay.Results: The results showed that CUMS rats had typical depressive behaviors, and the expression of miR-144 in the hippocampus of CUMS rats was significantly lower than that of the control group. In addition, PTP1B protein expression was significantly up-regulated, while the expression of pTrkB and BDNF protein was significantly down-regulated in the hippocampus of CUMS rats. Moreover, PTP1B was a direct target of miR-144, and miR-144 could activate the downstream TrkB/BDNF signaling pathway by inhibiting the expression of PTP1B in primary hippocampus neurons.Conclusion: MiR-144 played an anti-depressive role in hippocampus dysfunction by inhibiting PTP1B and activating the TrkB/BDNF signaling pathway in the hippocampus of CUMS rats.Keywords: miR-144, CUMS, hippocampus, PTP1B, TrkB/BDNF

Abstract Background Renal cell carcinoma (RCC) is a common urological cancer. circular RNAs (circRNAs) is involved in the development of various types of cancers. However, the roles and underlying mechanisms of circRNAs in RCC are not fully elucidated. Herein, we aimed to examine the potential effect of circ_001287 on RCC progression. Materials and Methods Microarray-based gene expression profiling of RCC was initially employed in order to identify differentially expressed genes. Next, the expression of circ_001287 was examined, and the cell line with the highest circ_001287 expression was selected for subsequent investigation. The interaction among circ_001287, miR-144, and CEP55 was identified by conducting luciferase reporter assay, RNA-pull down, RIP, RT-qPCR and FISH. The effect of circ_001287 on proliferative, invasive and migratory capacities as well as tumorigenicity of transfected cells in mice was examined using gain- and loss-of-function experiments. Results circ_001287 and CEP55 were highly expressed while miR-144 was decreased in RCC tissues and cell lines. circ_001287 can up-regulate CEP55 by binding to miR-144, which resulted in increased proliferative, invasive and migratory capacities and tumor growth in vivo. In addition, down-regulation of miR-144 was also observed to promote these biological activities. Conclusions Overall, these results elucidate a new mechanism for circ_001287 in RCC development and provide a potential therapeutic target for RCC patients.

Abstract Background Preeclampsia (PE) is a prevalent pregnancy disorder that has been one of the leading causes of maternal and perinatal mortality worldwide. Circular RNAs (circRNAs) have recently considered as important regulators in PE pathogenesis. In the current study, we aimed to explore the impact and mechanisms of circRNA zinc finger DHHC-type palmitoyltransferase 20 (circZDHHC20) in PE pathogenesis. Methods RNase R assay and reverse transcription with Oligo(dT)18 primers were performed to confirm that circZDHHC20 was indeed circular transcript. The expression of circZDHHC20, grainyhead-like 2 (GRHL2) and miR-144 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular localization assay was used to determine whether circZDHHC20 was predominantly present in the cytoplasm. The target correlations between miR-144 and circZDHHC20 or GRHL2 were confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell proliferation, migration, and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS), wound healing and transwell assays, respectively. Western blot was used for the quantification of GRHL2 protein level. Results Our data indicated that circZDHHC20 was up-regulated and miR-144 was down-regulated in PE placenta. CircZDHHC20 sequestered miR-144 by acting as a miR-144 sponge. CircZDHHC20 overexpression repressed trophoblast cell proliferation, migration, and invasion, while its knockdown exerted opposite effects. Moreover, miR-144 mediated the regulation of circZDHHC20 on trophoblast cell behaviors. GRHL2 was directly targeted and inhibited by miR-144. MiR-144 exerted regulatory effects on trophoblast cell proliferation, migration and invasion by GRHL2. Furthermore, circZDHHC20 modulated GRHL2 expression through sponging miR-144. Conclusion Our study suggested that a high level of circZDHHC20 inhibited the proliferation, migration, and invasion in trophoblast cells at least partially through sponging miR-144 and up-regulating GRHL2, providing a novel mechanism of PE pathogenesis.

The aim of the present study was to investigate the expression of AXL and mTOR genes and their targeting microRNAs (miRNAs) including miR-34a and miR-144 in Medullary Thyroid Carcinoma (MTC) cell line, TT, and determine the effect of these two miRNAs on their target genes to introduce new molecular markers or therapeutics. The expression of miR-34a, miR-144, and their targets genes including AXL and mTOR was evaluated by quantitative Real-time PCR. Luciferase assay was performed to confirm the interaction between miRNAs and their target mRNAs. The expression level of AXL and mTOR was evaluated before and after miRNAs induction in TT cell line compared with Cos7 as control cells. The expression of AXL and mTOR were up-regulated significantly, while miR-34a and miR-144 were down-regulated in TT cell line compared to Cos7. After transduction, the overexpression of miR-34a and 144 caused down-regulation of both genes. Luciferase assay results showed that the mTOR is targeted by miR-34a and miR-144 and the intensity of luciferase decreased in the presence of miRNAs. Based on the results of the present study and since AXL and mTOR genes play a critical role in variety of human cancers, suppression of these genes by their targeting miRNAs, especially miR-34a and miR-144, can be propose as a new strategy for MTC management. However, more studies are needed to approve the hypothesis. [ABSTRACT FROM AUTHOR]

Recently, therapeutic effects of extremely low-frequency electromagnetic field (ELF-EMF) as complementary and alternative medicine, used in the oncology field to control disease symptoms. Micro RNAs (miRs) are responsible for the post-transcriptional regulation of gene expression in the cell. This study aimed to evaluate the expression changes of miR-144 and miR-375 in the human gastric adenocarcinoma cell line (AGS) under the exposure of ELF-EMF. AGS cells were exposed to magnetic flux densities of 0.2 and 2 mT for 18 h, continuously and discontinuously (1.5 h on/1.5 h off). Cell viability was evaluated by MTT assay. Changes of miR-144 expression levels in AGS cells immediately after exposure and 18 and 36 h after the exposure cut-off was calculated by QRT-PCR. The cell viability of AGS cells was decreased under the exposure of 0.2 and 2 mT EMFs when compared to the control. Up-regulation of miR-144 and miR-375 were observed in AGS cells under the exposure of magnetic fields. The results indicated that the miR levels were significantly decreased 18 and 36 h after finishing the exposure, but not reached the normal range. The results of this investigation indicated that weak and moderate intermittent 50 Hz ELF-EMFs can induce changes in miRNA expression. [ABSTRACT FROM AUTHOR]

Introduction: MicroRNAs (miRNAs) are endogenous small noncoding RNA molecules involved in modulation of cancer progression. Here, we investigated the possible role of miR-144 in non-small cell lung cancer (NSCLC) development.Material and Methods: The expression of miR-144 and TLR2 in NSCLC tissue and cell lines was determined by quantitative real-time PCR (qPCR). The TargetScan database was used to predict potential target genes of miR-144. Luciferase assay was used to verify the interaction between TLR2 and miR-144. TLR2 protein expression was measured by western blot. The secretion of interleukin (IL)-1β, IL-6 and IL-8 in A549 cells was detected by an ELISA kit. Cell migration and invasion were evaluated by wound healing assay and transwell assay, respectively.Results: Our results showed that miR-144 was downregulated in NSCLC tissue and cell lines when compared with the normal tissues and cell line (p < 0.05). The protein level of TLR2 in NSCLC tissue and cell lines was significantly higher than that in normal lung tissues. Dual luciferase reporter gene assay showed that miR-144 could bind to the 3'UTR of TLR2 specifically. Up-regulation of miR-144 significantly decreased the expression of TLR2. Up-regulation of miR-144 or down-regulation of TLR2 could decrease cell migration, invasion and secretion of IL-1β, IL-6 and IL-8 in A549 cells. Moreover, overexpression of TLR2 rescued the inhibitory effects of miR-144 on migration, invasion and inflammatory factor secretion of A549 cells.Conclusions: miR-144 could inhibit the migration, invasion and secretion of IL-1β, IL-6 and IL-8 through downregulation of TLR2 expression in A549 cells. [ABSTRACT FROM AUTHOR]

The continuous rise in relapse rate and mortality for multiple myeloma (MM) demands an effective treatment option. The microRNAs are emerging nowadays for their promising therapeutic potential. Earlier, we reported involvement of Versican (VCAN) in myeloma pathogenesis which could be inhibited by miR-144 and miR-199 in stroma. However, there is dearth of literature showcasing the direct effect of these miRs in association with VCAN in MM. Expression of miR-144 and miR-199 was determined in myeloma cell lines (RPMI8226 & U266). These miRs were inhibited by small oligos to elucidate changes in expression of VCAN along with variation in parameters such as proliferation, apoptosis, migration and invasion in vitro. Moreover, effect on certain downstream signaling cascades was also evaluated. Lastly, interaction of miRs with VCAN was assessed by reporter luciferase assay. microRNAs expression were found significantly elevated in myeloma cells in comparison to stromal levels reported previously. The antagomirs-mediated inhibition of miR-144 and miR-199 significantly induced VCAN expression in myeloma cells along with alteration in myeloma-associated parameters in favor of myeloma pathogenesis with downstream activation of FAK/STAT3 signaling. Interestingly, miR-144 found to have direct binding with VCAN 3′ UTR while miR-199 possess different mechanism. The inhibition of miR-144 and miR-199 contributed in myeloma progression via upregulation of VCAN in vitro affirming the translational significance of VCAN and associated microRNAs in MM. These miRs, hence might be employed for targeting VCAN and might emerge as an effective therapy for the better outcome of MM in clinical settings in future. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of microRNA-144 (miR-144) on the proliferation, migration, invasion and phosphoinositide-3 kinase (PI3K) pathway of pancreatic cancer SW1990 cells. Methods The expression of miR-144 in human normal pancreatic epithelial cell line HPDE and pancreatic cancer cells SW1990 were detected by RT-qPCR. SW1990 cells were transfected with miR-144 negative control plasmid (negative transfection group) and miR-144 mimic plasmid (miR-144 overexpression group), and untreated cells were taken as blank control group. The expression level of miR-144 in each group was detected by RT-qPCR. CCK-8 assay was used to detect cell proliferation. Plate clone formation assay was used to detect colony formation. Transwell assay was used to detect cell migration and invasion. The expression levels of PI3K and phosphorylated protein (p-PI3K), serine-threonine protein kinase (Akt) and phosphorylated protein (p-Akt) proteins in PI3K pathway were detected by Western blot. Results The expression level of miR-144 in SW1990 cells was significantly lower than that in HPDE cells (P < 0.05). The expression level of miR-144 in miR-144 overexpression group was significantly higher than those in blank control group and negative transfection group (P < 0.05). Cells proliferation rate, colony formation, the number of migration and invasion cells and the expression levels of p-PI3K and p-Akt proteins in the overexpression group were significantly lower than those in the blank control group and negative transfection group (all P < 0.05). Conclusion miR-144 is lowly expressed in pancreatic cancer cells SW1990. The up-regulation of miR-144 expression could effectively inhibit the proliferation, migration and invasion of pancreatic cancer cells, which may be related to the inhibition of PI3K pathway.

Binge consumption of alcohol results in severe global health problem. This study aimed to explore the potential efficacy of nuciferine (NCF) in protecting acute alcohol-induced liver injury and the underlying molecular mechanisms. We revealed that NCF activated Nrf2/HO-1 signaling in HepG2 hepatocytes and relieved alcohol-induced ROS generation and subsequent cell death. Mechanistically, suppression of miR-144 expression contributed to NCF-mediated activation of Nrf2/HO-1 signaling. Consistently, NCF modulated hepatic miR-144/Nrf2/HO-1 axis and alleviated acute alcohol-induced liver injury as well as concomitant oxidative stress and inflammation in mice. In addition, suppressing the catalytic activity of HO-1 by ZnPP, an inhibitor of HO-1, diminished the hepatoprotective effects of NCF. The ameliorative effects of NCF on acute alcohol-provoked hepatic oxidative stress and inflammation were also crippled by ZnPP. Taken together, our data suggested that NCF is able to relive acute alcohol-induced liver injury and modulating miR-144/Nrf2/HO-1 cascade is implicated in the hepatoprotective activity of NCF.

Background: Long non-coding RNA (lncRNA) distal-less homeobox 6 antisense 1 (DLX6-AS1) was reported to be dysregulated in lung cancer. However, detailed roles of DLX6-AS1 in the pathogenesis of non-small cell lung cancer (NSCLC) were largely unknown. Methods: The expression of DLX6-AS1 was measured in NSCLC tissues and cells by quantitative real-time PCR (qRT-PCR). The abundance of proline rich 11 (PRR11) were detected by qRT-PCR and western blot, respectively. The effects of DLX6-AS1 and PRR11 on cell proliferation, migration, invasion and apoptosis were explored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell and flow cytometry analysis, respectively. Luciferase reporter assay, qRT-PCR and western blot were performed to confirm the interaction between miR-144 and DLX6-AS1 or PRR11. Tumor xenograft assay was performed to verify the role of DLX6-AS1 in NSCLC in vivo. Results: DLX6-AS1 and PRR11 were elevated in NSCLC tissues and cells. DLX6-AS1 was positively correlated with PRR11 mRNA expression in NSCLC tissues. Knockdown of DLX6-AS1 and PRR11 significantly suppressed cell proliferation, migration and invasion and induced apoptosis in NSCLC cells, which was reversed by PRR11 overexpression. In addition, DLX6-AS1 and PRR11 were demonstrated to interact with microRNA-144 (miR-144) and DLX6-AS1 upregulated PRR11 expression by acting as a competing endogenous RNA (ceRNA) of miR-144 in NSCLC cells. Furthermore, DLX6-AS1 knockdown suppressed tumor growth in NSCLC in vivo by upregulating miR-144 and downregulating PRR11. Conclusion: Knockdown of DLX6-AS1 inhibited cell proliferation, migration, invasion and promoted apoptosis by downregulating PRR11 expression and upregulating miR-144 in NSCLC.

Objectives: Recent studies have revealed that circular RNA (circRNA) plays a pivotal role in cancer development. The study aimed to investigate the role of circ_0081146 in gastric cancer (GC). Results: Circ_0081146 was upregulated in GC tissues and cells. Patients with high expression of circ_0081146 had a significantly reduced 5-year overall survival rate. Circ_0081146 knockdown restrained the growth, migration and invasion of GC cells in vitro as well as tumorigenesis in vivo. Circ_0081146 targeted miR-144 and HMGB1 was targeted by miR-144. Circ_0081146 was negatively correlated with miR-144 expression, while positively correlated with HMGB1 expression in GC tissues. Moreover, the inhibitory effect of circ_0081146 knockdown on the progression of GC cells were reversed by silencing miR-144 or HMGB1 overexpression. Mechanically, circ_0081146 increased HMGB1 expression by targeting miR-144. Conclusion: Circ_0081146 functions as an oncogene in GC to promote cell growth, migration and invasion via modulating the miR-144/HMGB1 axis. [ABSTRACT FROM AUTHOR]

Background & Aims: Hepatocellular carcinoma (HCC) is among the malignancies with the highest mortality. The key regulators and their interactive network in HCC pathogenesis remain unclear. Along with genetic mutations, aberrant epigenetic paradigms, including deregulated microRNAs (miRNAs), exert profound impacts on hepatocyte transformation and tumor microenvironment remodeling; however, the underlying mechanisms are largely uncharacterized. Methods: We performed RNA sequencing on HCC specimens and bioinformatic analyses to identify tumor-associated miRNAs. The miRNA functional targets and their effects on tumor-infiltrating immune cells were investigated. The upstream events, particularly the epigenetic mechanisms responsible for miRNA deregulation in HCC, were explored. Results: The miR-144/miR-451a cluster was downregulated in HCC and predicted a better HCC patient prognosis. These miRNAs promoted macrophage M1 polarization and antitumor activity by targeting hepatocyte growth factor (HGF) and macrophage migration inhibitory factor (MIF). The miR-144/miR-451a cluster and EZH2, the catalytic subunit of polycomb repressive complex (PRC2), formed a feedback circuit in which miR-144 targeted EZH2 and PRC2 epigenetically repressed the miRNA genes via histone H3K27 methylation of the promoter. The miRNA cluster was coordinately silenced by distal enhancer hypermethylation, disrupting chromatin loop formation and enhancer-promoter interactions. Clinical examinations indicated that methylation of this chromatin region is a potential HCC biomarker. Conclusions: Our study revealed novel mechanisms underlying miR-144/miR-451a cluster deregulation and the crosstalk between malignant cells and tumor-associated macrophages (TAMs) in HCC, providing new insights into HCC pathogenesis and diagnostic strategies. [ABSTRACT FROM AUTHOR]

Patulin (PAT) is a mycotoxin produced by various fungal species that commonly contaminate apples and other fruit products. PAT is associated with glutathione (GSH) depletion and oxidative stress. Cytoprotective and antioxidant (AO) enzymes limit toxic outcomes and confer resistance to oxidative stress by influencing the expression of cytoprotective genes. The induction of these genes is tightly regulated by transcription factor nuclear factor erythroid 2 p45–related factor 2 (NRF2), a potential target of microRNA (miR)-144. This study aims to determine a possible role for miR-144 in NRF2 pathway activation following PAT exposure in human embryonic kidney (HEK293) cells. HEK293 cells were exposed to varying PAT concentrations (0, 0.2, 0.5, 1 μmol/L; 24 h). Protein expression of Keap1, NRF2, and phosphorylated (p) NRF2 (ser40) was quantified using western blotting. Gene expression of NRF2, SOD2, CAT, GPx, NQO1, GSTA1, HMOX, and miR-144 were evaluated by qPCR. PAT significantly decreased miR-144 (p = 0.0249) and concomitantly increased NRF2 protein expression, stability, and activation as evidenced by increased pNRF2 (p = 0.0216) expression and decreased total NRF2 (p = 0.0237). This was consistent with qPCR data which showed increased transcript levels of NRF2 (p = 0.0378) as well as the target genes CAT (p = 0.0273), NQO1 (p = 0.0156), HMOX (p = 0.0249), and GSTA1 (p = 0.0237). No changes were observed in Keap1 expression (p = 0.6444). This study implicates microRNAs in a mechanistic role in PAT-induced toxicity. PAT decreased miR-144 expression leading to NRF2 pathway activation and elevated AO gene expression. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Retinoblastoma (RB) is a highly malignant eye tumor with a low survival rate and a high metastatic rate. The current work was designed to investigate the potential roles of microRNA-144 (miR-144) in the diagnosis and prognosis of RB. METHODS: miR-144 expression levels in RB tissues and adjacent normal tissues, as well as serum samples from RB patients and healthy controls were measured. The association between miR-144 expression levels and clinical features were analyzed. Moreover, diagnostic and prognostic values of miR-144 in RB were verified by receiver operating characteristic analysis and Kaplan-Meier survival assays. RESULTS: The expression level of miR-144 was markedly decreased in tumor tissues of RB patients, and the expression level of miR-144 was positively associated with tumor size and metastasis in RB patients. Moreover, miR-144 can distinguish tumor tissues from normal tissues with high specificity and sensitivity, and RB patients with lower miR-144 expression have shorter overall and disease-free survival rates than those with higher miR-144 expression. Alternatively, miR-144 also decreased in the serum of RB patients in comparison with healthy subjects, and miR-144 expression levels in the tissue samples and serum were positively correlated. Furthermore, miR-144 levels in the serum of RB patients sensitively distinguished RB patients from healthy controls. CONCLUSIONS: miR-144 expression was downregulated in serum and tissue samples of RB patients and may function as a diagnostic and prognostic marker for RB.

Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC.

سالمندی با تغییراتی در کلسترول خون و به‌دنبال آن، بیماری‌های قلبی- عروقی همراه است. هدف این پژوهش، بررسی تأثیر دو نوع تمرین تناوبی و تداومی بر MicroRNAهای مرتبط با انتقال معکوس کلسترول در موش‌های سالمند بود. تعداد 30 سر موش صحرایی نر نژاد ویستار مسن (23 ماه) با میانگین وزنی 75/441 گرم به‌صورت تصادفی در دو گروه تمرینی و یک گروه کنترل شامل گروه تمرین تداومی (تعداد = 10)، تمرین تناوبی (تعداد = 10) و گروه کنترل (تعداد = 10) قرار گرفتند. تمرین تداومی و تناوبی شامل هشت هفته تمرین روی تردمیل و پنج روز در هفته بود که گروه تداومی تمرین را با 60 درصد سرعت بیشینه و به‌مدت 16 دقیقه در هفتة اول شروع کردند و با 70 درصد سرعت بیشینه و مدت 45 دقیقه از هفتة چهارم به بعد ادامه دادند. گروه تناوبی تمرین را با شدت 40 تا 80 درصد سرعت بیشینه از هفتة اول شروع کردند و با30 تا 110 درصد سرعت بیشینه از هفتة چهارم به بعد ادامه دادند. بعد از دورة تمرین، بیان miR-33a و miR-144 و بیان ژن ABCA1 به روش RT –PCR اندازه‌گیری شد. تجزیه‌وتحلیل آماری با استفاده از آزمون آنوا با سطح معنا­داری P < 0.05 انجام شد. نتایج نشان داد که بیان miR-33a و miR-144 در دو گروه تداومی و تناوبی نسبت به گروه کنترل کاهش داشتند؛ اما این کاهش در هر دو گروه نسبت به گروه کنترل تنها درموردmiR-33a معنا‌دار بود (P < 0.001). بیان mRNA ژن ABCA1 در گروه تداومی و تناوبی پس از هشت هفته تمرین نسبت به گروه کنترل افزایش داشت؛ بااین‌وجود، این افزایـش تنـها در گـروه تناوبی نسـبت به گـروه کنتـرل مـعنـادار بـود (P = 0.002). بین تأثیر تمرین تناوبی و تداومی بر بیان miR-33a و miR-144 تفاوت معنا‌داری وجود نداشت؛ اما درمورد بیان mRNA ژن ABCA1 تفاوت معنا­داری در دو گروه تداومی و تناوبی مشاهده شد (P = 0.028). با توجه به نتایج این مطالعه، به‌نظر می‌رسد که هر دو تمرین استقامتی تناوبی و تداومی می‌توانند باعث کاهش بیان miR-33a و به‌دنبال آن، افزایش بیان mRNA ژن ABCA1 شوند؛ اما این افزایش در تمرین تناوبی نسبت به تمرین تداومی بیشتر است.

The regulation of globin gene expression is significantly important to understand the pathogenesis of globin gene disorders. Recent findings have shown that microRNAs (miRNAs, miRs) play an important role in the regulation of globin gene expression. The miR-144 is an erythroid lineage-specific miRNA, in which its expression mediates NRF2 gene silencing and inhibits fetal hemoglobin expression. However, roles of miR-144 to other globin genes expression especially in α-globin cluster remain unknown. This study, thus, examined the functional studies of miR-144 to globin gene expression in K562 human erythroid cell line. The results revealed that α-globin and ζ-globin gene expression were silenced by the overexpressed miR-144 and that correlated with the reduced expression of KLF1- the suspected target gene. By contrast, transfection with miR-144 inhibitor reversed the silencing effect of miR-144. On the other hand, miR-144 had no effect to β-globin gene expression. Our results sustain the findings of the previous studies that the overexpression of miR-144 correlates with the repressing of NRF2 and γ-globin gene expression. Taken together, our results suggest that miR-144 plays a key role in globin gene expression by silencing γ-globin through NRF2 target mRNA and repressing adult α-globin and embryonic ζ-globin gene expression possibly by targeting KLF1 gene. [ABSTRACT FROM AUTHOR]

OBJECTIVE: MicroRNAs (miRNA) are aberrantly expressed in various human cancers, including colorectal cancer (CRC). We aim to investigate the functional role and underlying mechanism of miR-144 in CRC. PATIENTS AND METHODS: The expressional level of miR-144 and pre-leukemia transcription factor 3 (PBX3) in CRC tissues and cells was confirmed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. The migration and invasion of CRC cells were detected by transwell assay. Luciferase reporter assay was performed to determine the specific target of miR-144 in CRC cells. RESULTS: The results displayed that miR144 expression was significantly decreased in CRC tissues and cells compared to that in normal controls. Additionally, miR-144 mimic suppressed, while miR-144 inhibitor promoted the ability of CRC cell migration and invasion. More importantly, PBX3 was the direct target of miR-144 in regulating CRC development and PBX3 could reverse the inhibitory effect of miR144 mimic on CRC cells. PBX3 expression was significantly increased in CRC and negatively correlated with miR-144 expression. CONCLUSIONS: In conclusion, miR-144 suppressed CRC cell migration and invasion by targeting PBX3, suggesting its potential value in the diagnosis and treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been revealed to be important regulators in the biological behavior of cells, and aberrant circRNAs may be associated with the etiology of pre-eclampsia (PE). However, the role and underlying molecular mechanisms of circ_0085296 in PE remain unclear.Methods: The expression of circ_0085296, microRNA (miR)-144, and E-cadherin was detected using quantitative real-time polymerase chain reaction and western blot, respectively. Cell proliferation, migration, and invasion were analyzed by cell counting kit-8, colony formation and transwell assay. The interaction between miR-144 and circ_0085296 or E-cadherin was analyzed by the dual-luciferase reporter assay and pull-down assay.Results: Circ_0085296 was elevated in PE placental tissues, knockdown of circ_0085296 promoted trophoblast cell proliferation, invasion, and migration, while circ_0085296 up-regulation showed opposite effects. MiR-144 was down-regulated in PE placental tissues, and restoration of miR-144 induced proliferation, invasion, and migration in trophoblast cells. Further mechanistic analysis found miR-144 directly bound to circ_0085296 and E-cadherin, and circ_0085296 functioned as a sponge of miR-144 to regulate E-cadherin expression. Furthermore, miR-144 inhibition or E-cadherin overexpression attenuated the effectsof circ_0085296 on cell processes in trophoblast cells.Conclusion: Circ_0085296 inhibited trophoblast cell proliferation, invasion, and migration via regulating miR-144/E-cadherin axis, providing a novel insight into the pathogenesis of PE and a new prospective therapeutic target for PE patients. [ABSTRACT FROM AUTHOR]

Previously, we found that the expression of long non-coding RNA (lncRNA) small nucleolar RNA host gene 17 (SNHG17) was up-regulated in castration-resistant prostate cancer (CRPC) cells compared to that in hormone sensitive prostate cancer (HSPC) cells. Moreover, we found that CD51 was up-regulated in prostate cancer cells and promoted the carcinogenesis and progression of prostate cancer. However, the regulatory mechanism of SNHG17 and CD51 in the development of CRPC remains unclear. In the current study, we aimed to elucidate the expressions, functions, and underlying mechanism of SNHG17 and CD51 in CRPC. Our results further confirmed that both SNHG17 and CD51 were up-regulated in CRPC tissues and cells. In addition, we found that SNHG17 expression was positively correlated with CD51 expression in prostate cancer. Mechanically, SNHG17 functioned as a competing endogenous RNA (ceRNA) to up-regulate CD51 expression through competitively sponging microRNA-144 (miR-144), and CD51 was identified as a direct downstream target of miR-144 in CRPC. Functionally, down-regulation of SNHG17 or up-regulation of miR-144 inhibited the proliferation, migration, and invasion of CRPC cells, whereas up-regulation of SNHG17 and down-regulation of miR-144 promoted the proliferation, migration and invasion of CRPC cells in vitro and in vivo. Using gain and loss-of function assay and rescue assay, we showed that miR-144 inhibited cell proliferation, migration and invasion by directly inhibiting CD51 expression, and SNHG17 promoted cell proliferation, migration and invasion by directly enhancing CD51 expression in CRPC cells. Taken together, our study reveals the role of the SNHG17/miR-144/CD51 axis in accelerating CRPC cell proliferation and invasion, and suggests that SNHG17 may serve as a novel therapeutic target for CRPC. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma (OS) is a common bone tumor among children, adolescents, and young adults. Long non-coding RNA (lncRNA) FEZF1 antisense RNA 1 (FEZF1-AS1) has been reported as an oncogene in diverse tumors including colorectal cancer, pancreatic cancer and hepatocellular carcinoma, as well as in osteosarcoma. This study focused on the functions and mechanism of lncRNA FEZF1-AS1 in osteosarcoma. Methods: The levels of FEZF1-AS1, microRNA miR-144 and CXC motif chemokine receptor 4 (CXCR4) in OS tissues and cells (Saos-2 and HOS) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The interactions between miR-144 and FEZF1-AS1 or CXCR4 were predicted by DIANA tools online database. Then, the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to validate the interactions. Moreover, the cell viability and apoptotic rate in transferred Saos-2 and HOS cells were assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry, respectively. The levels of glucose and lactate productions were measured by glucose uptake and lactate production assay. In addition, the protein levels of Warburg-effect-related protein hexokinase 2 (HK2) and apoptosis-related proteins Bcl-2 or Bax in transferred Saos-2 and HOS cells were detected via Western blot assay. Results: The levels of FEZF1-AS1 and CXCR4 were strikingly up-regulated, and miR-144 was notably down-regulated in OS tissues and cells. DIANA tools online database exhibited that miR-144 was a direct target of FEZF1-AS1 and CXCR4 was a direct target of miR-144. Then the interactions were validated by dual-luciferase reporter assay and RIP assay. Functionally, FEZF1-AS1 silencing or miR-144 overexpression inhibited cell viability, the glucose and lactate productions and promoted cell apoptosis in Saos-2 and HOS cells. Furthermore, miR-144 inhibitor mitigated the inhibitory effects on cell viability, the glucose and lactate productions and the promoted effect on cell apoptosis rate in Saos-2 and HOS cells induced by FEZF1-AS1 depletion. Mechanistically, FEZF1-AS1 regulated CXCR4 in Saos-2 and HOS cells by sponging miR-144. Conclusion: We verified that FEZF1-AS1, CXCR4 were up-regulated, and miR-144 was downregulated in OS tissues and cells. Furthermore, FEZF1-AS1 promoted cell proliferation, Warburg effect and suppressed cell apoptosis in osteosarcoma via miR-144/CXCR4 axis, this novel pathway may provide a basis for the further study of osteosarcoma. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been shown to participate in development of neuropathic pain. However, the role of microRNA‐144 (miR‐144) in neuropathic pain remains unclear. In the present study, we established a neuropathic pain mouse model via chronic constriction injury (CCI)‐induction. The successful establishment of this model was confirmed via evaluation of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). By using this model, we found that miR‐144 was significantly downregulated in CCI‐induced neuropathic pain mice. In addition, intrathecal injection of miR‐144 agomiR alleviated mechanical and thermal hyperalgesia in neuropathic pain mice as shown by the increased of PWT and PWL. Moreover, miR‐144 negatively regulated neuroinflammation by decreasing the expression of proinflammatory mediators, including TNF‐α (tumor necrosis factor‐α), IL (interleukin)‐1β, and IL‐6, thus facilitating the inhibition of neuropathic pain development. Mechanistically, RASA1 (RAS P21 Protein Activator 1) was downregulated following the injection of agomiR‐144, and was verified to be a target of miR‐144. Furthermore, overexpression of RASA1 reversed the inhibitory effect of miR‐144 on neuropathic pain. Therefore, the present study suggested that miR‐144 has the potential to be explored as therapeutic target for treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Several lines of evidence have revealed the potential of microRNAs (miRNAs, miRs) as biomarkers for detecting diabetic cardiomyopathy, although their functions in hyperglycemic cardiac dysfunction are still lacking. In this study, mitochondrial biogenesis was markedly impaired induced by high glucose (HG), as evidenced by dysregulated mitochondrial structure, reduced mitochondrial DNA contents, and biogenesis‐related mRNA levels, accompanied by increased cell apoptosis. MiR‐144 was identified to be decreased in HG‐induced cardiomyocytes and in streptozotocin (STZ)‐challenged heart samples. Forced miR‐144 expression enhanced mitochondrial biogenesis and suppressed cell apoptosis, while miR‐144 inhibition exhibited the opposite results. Rac‐1 was identified as a target gene of miR‐144. Decreased Rac‐1 levels activated AMPK phosphorylation and PGC‐1α deacetylation, leading to increased mitochondrial biogenesis and reduced cell apoptosis. Importantly, the systemic neutralization of miR‐144 attenuated mitochondrial disorder and ventricular dysfunction following STZ treatment. Additionally, plasma miR‐144 decreased markedly in diabetic patients with cardiac dysfunction. The receiver‐operator characteristic curve showed that plasma miR‐144 could specifically predict diabetic patients developing cardiac dysfunction. In conclusion, this study provides strong evidence suggesting that miR‐144 protects heart from hyperglycemia‐induced injury by improving mitochondrial biogenesis and decreasing cell apoptosis via targeting Rac‐1. Forced miR‐144 expression might, thus, be a protective strategy for treating hyperglycemia‐induced cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) is a scarce cancerous disease, originating from parafollicular C cells of the thyroid gland. MTC can be manifested as an aggressive carcinoma with metastasis, especially in sporadic forms. Mutations of the rearranged during transfection (RET) proto‐oncogene occurs in all hereditary and a few somatic MTCs, so detection of RET mutations is needed for prompt and appropriate treatment. MicroRNAs (miRNAs) are noncoding regulatory RNAs. Extensive studies have done in progress or suppression of several types of cancers such as MTCs with the remarkable application as prognostic markers. Of the effective miRNAs in cancers, miR‐144 and miR‐34 were evaluated in our study. Blood samples of 25 RET‐positive and 25 RET‐negative blood samples of patients with MTC were evaluated for these miRNAs, using quantitative real‐time polymerase chain reaction (RT‐qPCR). Analysis of the results was performed by the 2 −ΔΔCt method, showing that miR‐144 and miR‐34a expression had a relative increase in patients with MTC compared with normal control samples and also in RET positives versus RET negatives. We recruited 50 out of 350 MTC plasma samples (27 female and 23 male) which were selected based on RET mutation in exon 11 (25 RET‐positive and 25 RET‐negative), with a mean ± SD age of 37.04 ± 1.74 years. Receiver operating characteristic (ROC) curve analysis was done to investigate the prognostic value of these miRNAs; although, they showed no significant prognostic value as MTC biomarkers in plasma samples. In conclusion, miRNAs can be used as biomarkers of cancers such as MTC; however, more studies are needed to find the best candidate miRNAs for the diagnosis of cancers. [ABSTRACT FROM AUTHOR]