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As the population ages, the prevalence of atherosclerosis (AS), a significant cause of cardiovascular disease (CVD), continues to increase. Apoptosis is an independent risk factor for atherosclerosis. Macrophages are the primary immune cell group in AS lesions, and their apoptosis plays a crucial role in the occurrence and development of AS. There is a common mechanism of action for circular RNAs (circRNAs) that involves the sponging of microRNAs (miRNAs) by binding to the miRNA response element (MRE), thereby increasing the transcription of their target messenger RNAs (mRNAs). Most diseases are profoundly reliant on circRNAs. However, the underlying mechanism of circRNAs in apoptosis is yet to be elucidated. All differentially expressed genes (DEGs) and their expression levels were analysed by whole-transcriptome sequencing of samples from the control and nicotine groups of THP-1 macrophages. GO and KEGG analyses revealed that nicotine affects macrophage physiological processes and related pathways. GSEA focused on gene sets to better understand the potential pathways and biological functions of all mRNAs. A competitive endogenous RNA (ceRNA) regulatory network was constructed and validated through molecular biology experiments. The Notch signalling pathway was activated in nicotine-treated macrophages, and the expression of DLL4 in this pathway was increased. Circ_0006476 is involved in apoptosis via miR-3074-5p / DLL4 , regulating pathogenic processes related to the Notch signalling pathway. The better we understand the pathways involved in macrophage apoptosis, the more likely we are to find other novel therapeutic targets that can help treat, prevent, and reduce the mortality associated with AS.

The purpose of this study was to construct a competitive endogenous RNA (ceRNA) network related to long non-coding RNA (lncRNAs) via the bioinformatics analysis, reveal the pathogenesis of coronary heart disease (CAD) and develop new biomarkers for CAD. The gene expression datasets of peripheral blood of CAD were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were identified. Subsequently, a ceRNA network involving lncRNAs, miRNAs, and mRNAs was built. Moreover, DElncRNAs in the cytoplasm were screened and a DElncRNA-associated ceRNA network was established. In total, 1860 DEmRNAs, 393 DElncRNAs and 20 DEmiRNAs were filtrated in patients with CAD compared with normal controls. Functional analysis suggested that DEmRNAs significantly enriched in CAD-related pathways, such as PI3K-Akt signaling pathways and MAPK signaling pathway. The ceRNA network contained 12 DEmiRNAs, 30 DElncRNAs and 537 DEmRNAs. Afterwards, the cytoplasm ceRNA network was consisted of 537 DEmRNAs, 12 DEmiRNAs and 12 DElncRNAs. Such as, up-regulated LncRNA-HOX transcript antisense RNA (HOTAIR) was interacted with down-regulated has-miR-326 and has-miR-1. The successful construction of lncRNA-associated ceRNA network is helpful to better clarify the pathogenesis of CAD and provide potential peripheral blood biomarkers for CAD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To explore the effect of miR-125b-5p/nuclear factor of activated T cells 1 ( NFAT2 )/ F2RL2 on myocardial infarction (MI). Method: After establishment of MI mouse model and oxygen glucose deprivation (OGD)-induced cell model, the effects of NFAT2 on the process of MI were observed, the effects of miR-125b-5p/ NFAT2 / F2RL2 on the cell viability, apoptosis, and inflammatory factors levels were determined. Result: NFAT2 silencing relieved MI and inhibited the inflammation in MI model mice. In OGD-induced human coronary artery endothelial cells and human cardiac microvascular endothelial cells, miR-125b-5p enhanced cell viability, yet repressed cell apoptosis and inflammatory factors and NFAT2 levels. NFAT2 overexpression reversed the effects of miR-125b-5p, while F2RL2 silencing offset the effects of NFAT2 overexpression. Conclusion: MiR-125b-5p alleviates MI injury by inhibiting NFAT2 level to reduce F2RL2 expression.

Background: This study is aimed at effectively investigating the role of coagulation factor II thrombin receptor like 2 (F2RL2) in myocardial infarction (MI) as well as the upstream regulatory miRNA and lncRNA., Methods: Regulatory genes of F2RL2 were analyzed using StarBase and verified by dual-luciferase reporter assay. The MI mouse model was established. The left ventricular ejection fraction (EF) and fractional shortening (FS) were examined by echocardiography. The infarct area, pathological changes, and cell apoptosis in mouse myocardial tissue were evaluated using triphenyltetrazolium chloride and Evans blue, hematoxylin-eosin, and TUNEL staining assays. Oxygen-glucose deprivation- (OGD-) induced human cardiac myocytes (HCMs) were cultured and transfected. The cell viability, proliferation, and apoptosis were determined by CCK-8, EdU staining, and flow cytometry assays. The expressions of F2RL2, miR-582-5p, and nuclear paraspeckle assembly transcript 1 (NEAT1) in myocardial tissues and HCMs were quantified by qRT-PCR or Western blot., Results: NEAT1 sponged miR-582-5p which targeted F2RL2. NEAT1 and F2RL2 were highly expressed while miR-582-5p was lowly expressed in MI mice. F2RL2 downregulation prevented the reduction in EF and SF and the elevation in infarct area and cell apoptosis of MI mice. Both F2RL2 and NEAT1 downregulations reversely modulated the decreased viability and proliferation and the increased apoptosis of OGD-induced HCMs, while miR-582-5p inhibitor did oppositely. NEAT1 silencing upregulated miR-582-5p level but downregulated F2RL2 level. miR-582-5p inhibitor upregulated the F2RL2 level. The role of NEAT1 silencing in OGD-induced HCMs was reversed by miR-582-5p inhibitor whose effect was further offset by F2RL2 downregulation., Conclusion: NEAT1 downregulation ameliorates MI by regulating the miR-582-5p/F2RL2 axis, providing novel biomarkers for MI treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Zhenhua Wu et al.)

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.

Cardiovascular diseases seriously endanger human physical and mental health and life safety, to investigate correlation between miR-let-7b and miR-29b and coronary artery calcification of various patients. At present, real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression levels of plasma miR-let-7b and miR-29b in patients with coronary artery calcification and noncoronary artery calcification and to analyze whether the expression levels of miR-let-7b and miR-29b were different between the two groups. It was shown that there was no significant difference in the expression of miR-let-7d-3p between the two groups. But the expression of miR-29b in the observation group was significantly lower than that in the control group. Taken together, miR-29b might be a risk factor for coronary artery calcification and may be a marker for early diagnosis of coronary artery calcification., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Ning Yang et al.)

Atherosclerosis (AS) is the most dangerous factor for human death, which is a lipid-driven chronic inflammatory disorder of the arteries. Growing evidence has showed that microRNAs play an important role in AS. However, the role of mir-193b-3p in atherosclerosis has been poorly studied to date. Therefore, we focused on the potential role of miR-193b-3p in atherosclerosis. The expressions of miR-193b-3p in the serum of AS patients were detected. We also established an oxidized low density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) apoptosis model in vitro. The mRNA and protein levels of target molecules were detected by RT-qPCR and Western blotting. Apoptosis of HUVECs was determined by Annexin V/PI staining on a flow cytometry. The potential molecular targets of miR-193b-3p were investigated by applying such technologies as dual-luciferase reporter and RIP assay. Our study showed that miR-193b-3p expression level was significantly lower in AS patients than controls. ROC curve analysis showed that the areas under the curve (AUC) of plasma miR-193b-3p was 0.859. We also found that miR-193b-3p was decreased in ox-LDL-induced HUVECs and knockdown of miR-193b-3p suppressed ox-LDL-induced HUVECs injury. By using bioinformatics analysis, aldehyde dehydrogenase (ALDH2) was predicted as a downstream target of miR-193b-3p. The ALDH2 gene is also involved in the development of atherosclerosis. Meanwhile, inhibition of miR-193b-3p and ALDH2 protects ox-LDL-induced HUVECs against endoplasmic-reticulum (ER) stress. In conclusion, inhibition of miR-193b-3p was able to suppress ox-LDL-induced injury in AS through targeting ALDH2 and reducing ER stress., (© 2021 International Federation for Cell Biology.)

Atherosclerosis is generally accepted as a chronic inflammatory disease and is the most important pathological process underlying the cardiovascular diseases. MiR-22 exerts an important role in tumorgenesis, obesity and NAFLD development, as well as cardiovascular diseases. However, a certain role of miR-22 in the pathogenesis of atherosclerosis remains undetermined. Here, we showed that miR-22 exhibited a negative association with the deteriorated atherosclerotic plaque and showed significant downregulated expression in macrophages. Next, treatment of ApoE deficiency (ApoE -/- ) mice with miR-22 inhibitors which were then subjected to high fat diet (HFD) for 12 weeks were performed to investigate the function of miR-22 on atherogenesis. The results exhibited that miR-22 inhibition dramatically promoted atherosclerotic plaques but attenuated plaque stabilization which were accompanied by decreased smooth muscle cell and collagen content, but increased macrophage infiltration and lipid accumulation. More importantly, the in vivo and in vitro experiments suggested that miR-22 inhibition accelerated inflammatory response and foam cell formation. Mechanistically, we demonstrated interferon regulator factor 5 (IRF5) was an important target of miR-22 and it was required for the regulation of inflammation mediated by miR-22 inhibition. Collectively, these evidences revealed that miR-22 inhibition promoted the atherosclerosis progression through activation of IRF5., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell dysfunction is a significant event in the progression of atherosclerosis. Even Myricetin (Myr) has been exhibited strong antioxidant potency, the effect on atherosclerosis is still elusive. HUVECs were subjected to ox-LDL, before which cells were preconditioned with Myr. Cell Counting Kit-8 assay, flow cytometry, quantitative real-time polymerase chain reaction and Western blot were carried out to assess the impacts of ox-LDL and Myr on HUVECs. The expression of EndMT markers was determined by Western blot analysis and immunocytochemistry. In addition, the relationship of GAS5 and miR-29a-3p was evaluated by RNA Fluorescent in Situ Hybridization and RNA immunoprecipitation assay. Myr preconditioning prevented ox-LDL-induced apoptosis, inflammatory response, and EndMT. GAS5 was upregulated in response to ox-LDL while it was down-regulated by Myr preconditioning. GAS5 over-expression attenuates Myr protective effects against ox-LDL-mediated HUVEC injury. Besides, miR-29a-3p is a target of GAS5 and down-regulated miR-29a-3p could further reduce the effects of GAS5 in ox-LDL-mediated HUVEC. Furthermore, Myr inactivated the TLR4/NF-κB signalling pathway in ox-LDL-treated HUVEC by down-regulating GAS5 or upregulating miR-26a-5p. Myr possessed an anti-inflammatory and anti-EndMT function against ox-LDL-induced HUVEC injury by regulating the GAS5/miR-29a-3p, indicating that Myr may have an important therapeutic function for atherosclerosis., (© 2021. The Author(s).)

Atherosclerosis is a lipid-driven chronic inflammatory disease in which lipid-laden macrophage foam cells lead to inflamed lesions in arteries. Previous studies have proven that sulfotransferase 2B1b (SULT2B1b) has several roles in the regulation of lipid metabolism and the inflammatory response. However, little is known about the functions of SULT2B1b in ox-LDL-induced inflammation in macrophages. In this study, after treatment with either ox-LDL alone or combined with transfection of siRNAs targeting SULT2B1b, IL-6, TNF-α, NF-κB, IKKβ and IκB mRNA and protein expression were determined in Raw264.7 cells by real-time PCR and Western blot, respectively. The proliferative capacity was determined by EdU staining and Cell Counting Kit-8. Our data demonstrated that SULT2B1b knockdown could reduce phosphorylated NF-κB levels and downregulate IKKβ protein levels. Additionally, IκB levels were increased and the proliferation of ox-LDL stimulated cells was inhibited after SULT2B1b silencing. Downregulation of SULT2B1b expression was found to upregulate miR-148a-3p expression by microarray assay, while IKKβ was a miR-148a-3p target gene. Our study suggests that SULT2B1b knockdown could promote miR148a-3p expression and inhibit activation of the IKKβ/NF-κB signalling pathway, which suppressed the inflammatory response in macrophages. Therefore, targeting the SULT2B1b gene might be potentially beneficial for atherosclerosis prevention by decreasing the inflammatory response.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and has the highest mortality rate among cancers and high resistance to radiation and cytotoxic chemotherapy. Although some targeted therapies can partially inhibit oncogenic mutation-driven proliferation of GBM cells, therapies harnessing synthetic lethality are 'coincidental' treatments with high effectiveness in cancers with gene mutations, such as GBM, which frequently exhibits DNA-PKcs mutation. By implementing a highly efficient high-throughput screening (HTS) platform using an in-house-constructed genome-wide human microRNA inhibitor library, we demonstrated that miR-1193 inhibition sensitized GBM tumor cells with DNA-PKcs deficiency. Furthermore, we found that miR-1193 directly targets YY1AP1, leading to subsequent inhibition of FEN1, an important factor in DNA damage repair. Inhibition of miR-1193 resulted in accumulation of DNA double-strand breaks and thus increased genomic instability. RPA-coated ssDNA structures enhanced ATR checkpoint kinase activity, subsequently activating the CHK1/p53/apoptosis axis. These data provide a preclinical theory for the application of miR-1193 inhibition as a potential synthetic lethal approach targeting GBM cancer cells with DNA-PKcs deficiency.

Obesity is associated with an increased risk of developing insulin resistance (IR) and type 2 diabetes (T2D). A diverse group of factors including miRNA has been implicated in the pathogenesis of these two metabolic conditions, although underlying molecular mechanisms involved are not well defined. Here, we provide evidence that hepatic miR-125a levels are diminished in both genetic as well as dietary mouse models of obesity. Overexpression of miR-125a enhanced insulin signaling and attenuated cellular lipid accumulation in HepG2 cells and Hepa1-6 cells. Likewise, treatment of mice with ago-miR-125a increased insulin sensitivity, similar to overexpression of miR-125a, whereas treatment of mice with antago-miR-125a blunted the insulin sensitivity. Furthermore, overexpression of miR-125a in mice previously fed a high-fat diet (HFD), significantly improved insulin sensitivity, and attenuated obesity-linked hepatic steatosis and hepatocyte lipid accumulation. In addition, we show that ELOVL fatty acid elongase 6 (Elovl6) is a direct target of miR-125a, and participates in miR-125a mediated regulation of insulin sensitivity and lipid metabolism. These data led us to conclude that dysregulated miR-125a expression augments the development of obesity-induced IR and that miR-125a might serve as a therapeutic target for the development of new drug(s) in the clinical management of metabolic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Chidamide has a broad spectrum of antitumor activity but its function on glioma remains unknown. The increase of reactive oxygen species (ROS) and reactive nitrogen species (RNS) may control glioma risk by promoting its apoptosis and necrosis. Hedgehog pathway is crucial to glioma cell proliferation and controls ROS production. We aimed to explore the effects of chidamide on the levels of miR-338-5p (glioma cell inhibitor), which may regulate Hedgehog signaling, resulting in the changes of RNS. Materials and Methods . Migration and invasion activities of glioma cells were measured by using the Transwell chamber assay. The expression levels of Sonic Hedgehog (Shh), Indian Hedgehog (Ihh), Desert Hedgehog (Dhh), miR-338-5p, and related molecules were detected by using real-time PCR (RT-PCR) and or Western Blot in U87 and HS683 glioma cells. The effects of chidamide on these molecules were measured by using the miR-338-5p inhibitor or mimics in U87 and HS683 glioma cell lines. ROS and RNS were measured by DCF DA and DAF-FM DA fluorescence. Biomarkers of oxidative stress were measured by using a corresponding kit. Apoptosis and necrosis rates were measured by using flow cytometry., Results: Chidamide inhibited the growth rate, migration, and invasion of human malignant glioma cells and increased the level of miR-338-5p. miR-338-5p inhibitor or mimics increased or inhibited the growth rate of U87 and HS683 glioma cells. Chidamide inhibited the levels of Shh, Ihh, migration protein E-cadherin, and invading protein MMP-2. The increase in the level of Shh and Ihh led to the reduction in the ROS and RNS levels. miR-338-5p inhibitor or mimics also showed a promoting or inhibitory function for the levels of Shh and Ihh. Furthermore, miR-338-5p mimics and inhibitor inhibited or promoted the migration and invasion of the glioma cells ( P < 0.05). Evaluated levels of miR-338-5p increased oxidative stress level and apoptosis and necrosis rate by regulating the levels of biomarkers of oxidative stress ( P < 0.05). Evaluated levels of miR-338-5p increased oxidative stress level and apoptosis and necrosis rate by regulating the levels of biomarkers of oxidative stress (., Conclusion: Chidamide inhibits glioma cells by increasing oxidative stress via the miRNA-338-5p regulation of Hedgehog signaling. Chidamide may be a potential drug in the prevention of glioma development., Competing Interests: The authors declare that there are no other nonfinancial competing interests., (Copyright © 2020 Haixia Zhou et al.)

An increased DNA repair capacity is associated with drug resistance and limits the efficacy of chemotherapy in breast cancers. Flap endonuclease 1 (FEN1) participates in various DNA repair pathways and contributes to cancer progression and drug resistance in chemotherapy. Inhibition of FEN1 serves as a potent strategy for cancer therapy. Here, we demonstrate that microRNA-140 (miR-140) inhibits FEN1 expression via directly binding to its 3' untranslated region, leading to impaired DNA repair and repressed breast cancer progression. Overexpression of miR-140 sensitizes breast cancer cells to chemotherapeutic agents and overcomes drug resistance in breast cancer. Notably, ectopic expression of FEN1 abates the effects of miR-140 on DNA damage and the chemotherapy response in breast cancer cells. Furthermore, the transcription factor/repressor Ying Yang 1 (YY1) directly binds to the miR-140 promoter and activates miR-140 expression, which is attenuated in doxorubicin resistance. Our results demonstrate that miR-140 acts as a tumor suppressor in breast cancer by inhibiting FEN1 to repress DNA damage repair and reveal miR-140 to be a new anti-tumorigenesis factor for adjunctive breast cancer therapy. This novel mechanism will enhance the treatment effect of chemotherapy in breast cancer.

Glioma, an aggressive tumor in brain, presents a very poor prognosis. Emerging evidence has demonstrated that dysfunction of long noncoding RNAs (lncRNAs) is closely related to giloma development. However, the roles of lncRNA BLACAT1 in glioma are not unknown. In this study, we utilized in vitro and in vivo experiments to explore the effects of BLACAT1 on glioma cells. BLACAT1 levels were increased in glioma tissues. Upregulation of BLACAT1 showed poor prognosis. Silencing of BLACAT1 markedly repressed glioma proliferation, migration, and invasion, and suppressed glioma growth in vivo. We also illustrated that BLACAT1 worked as the sponge for miR-605-3p and promoted VASP expression. miR-605-3p was downregulated in glioma and repressed glioma proliferation, migration, and invasion. And VASP is upregulated and contributed to glioma progression. Summarily, this study highlights the important roles of BLACAT1/miR-605-3p/VASP axis in glioma progression., (© 2019 Wiley Periodicals, Inc.)

Flap endonuclease 1 (FEN1) is recognized as a pivotal factor in DNA replication, long-patch excision repair, and telomere maintenance. Excessive FEN1 expression has been reported to be closely associated with cancer progression, but the specific mechanism has not yet been explored. In the present study, we demonstrated that FEN1 promoted breast cancer cell proliferation via an epigenetic mechanism of FEN1-mediated up-regulation of DNA methyltransferase (DNMT)1 and DNMT3a. FEN1 was proved to interact with DNMT3a through proliferating cell nuclear antigen (PCNA) to suppress microRNA (miR)-200a-5p expression mediated by methylation. Furthermore, miR-200a-5p was identified to repress breast cancer cell proliferation by inhibiting the expression of its target genes, hepatocyte growth factor (MET), and epidermal growth factor receptor (EGFR). Overall, our data surprisingly demonstrate that FEN1 promotes breast cancer cell growth via the formation of FEN1/PCNA/DNMT3a complex to inhibit miR-200a expression by DNMT-mediated methylation and to recover the target genes expression of miR-200a, MET, and EGFR. The novel epigenetic mechanism of FEN1 on proliferation promotion provides a significant clue that FEN1 might serve as a predictive biomarker and therapeutic target for breast cancer.-Zeng, X., Qu, X., Zhao, C., Xu, L., Hou, K., Liu, Y., Zhang, N., Feng, J., Shi, S., Zhang, L., Xiao, J., Guo, Z., Teng, Y., Che, X. FEN1 mediates miR-200a methylation and promotes breast cancer cell growth via MET and EGFR signaling.

Scavenger Receptor B1 (SR-B1) is an 82 kDa integral membrane glycoprotein that mediates selective uptake of high-density lipoprotein cholesteryl ester (CE) in vitro and in vivo. Previously, we defined several kinds of regulatory mechanisms of SR-B1 expression and function. Here, we have dissected the function of a novel miR-24 on SR-B1 expression, HDL uptake and lipid metabolism. We showed that miR-24 was upregulated in HepG2 cells cultured in the mimicked hyperlipidemic condition and in the livers of dietary induced and genetic obesity mice. Overexpression of miR-24 inhibited SR-B1 expression by directly targeting SR-B1 3' UTR and repressed HDL uptake and steroidogenesis in steroidogenic cells. HepG2 cells with miR-24 showed attenuation of TG levels and lipid accumulation. Moreover, we validated that overexpression of miR-24 downregulated the expression of certain genes involved in lipogenesis, FASN, ACLY and SCD1, and increased the expression of genes of cholesterol synthesis, HMGCR, DHCR24 and SREBP2. Taken together, we demonstrated that obesity induced miR-24 repressed HDL uptake, steroid hormone synthesis and lipid metabolism by targeting SR-B1., (Copyright © 2018 Elsevier B.V. All rights reserved.)

MicroRNAs (miRNAs) are important gene regulators in both biological and pathological processes, including myocardial ischemia/reperfusion (I/R) injury. This study investigated the effect of miR-613 on I/R-induced cardiomyocyte apoptosis and its molecular mechanism of action. Hypoxia/reoxygenation (H/R) significantly increased the release of lactate dehydrogenase (LDH), levels of malondialdehyde (MDA), and cardiomyocyte apoptosis, but these effects were attenuated by an miR-613 mimic. Programmed cell death 10 (PDCD10) was identified as a target gene of miR-613. miR-613 significantly increased the phosphorylation of Akt (p-Akt). An miR-613 mimic lowered the level of expression of pro-apoptotic proteins, C/EBP homologous protein (CHOP), and phosphorylated c-Jun N-terminal kinase (p-JNK), and it up-regulated the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2). All of these effects were reversed by restoration of PDCD10. Taken together, the current findings indicate that miR-613 inhibits I/R-induced cardiomyocyte apoptosis by targeting PDCD10 by regulating the PI3K/AKT signaling pathway.

Hypoxia-induced cardiomyocyte apoptosis contributes significantly to the development of numerous cardiac diseases, such as ischemic heart disease, heart failure, etc. Promoting cell survival by inhibiting apoptosis is one of the available strategies to attenuate cardiac dysfunction caused by cardiomyocyte loss. Previous studies have been demonstrated that miR-138 and lipocalin-2 (Lcn2) play important roles in cardiomyocyte apoptosis and survival. We presently determined whether Lcn2 is a target gene of miR-138 involved in hypoxia-induced cardiomyocyte apoptosis. Firstly, mimics of miR-138 were transfected into HL-1 cells to investigate its effect on cell apoptosis. Using 3-(4,5-dimethyl-thiazol-2-y1) 2,5-diphenyl tetrazolium bromide (MTT) and Annexin V-FITC/PI flow cytometer assays, over-expression of miR-138 significantly enhanced the cell growth and significantly attenuated the cell apoptosis in hypoxic conditions. Dual-luciferase reporter gene and western blot results confirmed Lcn2 was a direct target of miR-138. Then, the recombinant plasmid, pcDNA3.1/Lcn2 was transfected into the HL-1 cells that over-expressed miR-138. We further observed that the over-expression of Lcn2 diminished the protection of miR-138 over-expression from hypoxia-induced cell survival and apoptosis. In conclusion, our study demonstrated that up-regulation of miR-138 inhibits the hypoxia-induced cardiomyocyte apoptosis via down-regulating the pro-apoptotic gene expression of Lcn2., (© 2016 by the Society for Experimental Biology and Medicine.)

The HOXB1 gene plays a critical role as an oncogene in diverse tumors. However, the functional role of HOXB1 and the mechanism regulating HOXB1 expression in glioma are not fully understood. A preliminary bioinformatics analysis showed that HOXB1 is ectopically expressed in glioma, and that HOXB1 is a possible target of miR-3175. In this study, we investigated the function of HOXB1 and the relationship between HOXB1 and miR-3175 in glioma. We show that HOXB1 expression is significantly downregulated in glioma tissues and cell lines, and that its expression may be closely associated with the degree of malignancy. Reduced HOXB1 expression promoted the proliferation and invasion of glioma cells, and inhibited their apoptosis in vitro, and the downregulation of HOXB1 was also associated with worse survival in glioma patients. More importantly, HOXB1 was shown experimentally to be a direct target of miR-3175 in this study. The downregulated expression of miR-3175 inhibited cell proliferation and invasion, and promoted apoptosis in glioma. The oncogenicity induced by low HOXB1 expression was prevented by an miR-3175 inhibitor in glioma cells. Our results suggest that HOXB1 functions as a tumor suppressor, regulated by miR-3175 in glioma. These results clarify the pathogenesis of glioma and offer a potential target for its treatment.