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1.
J Cell Biochem ; 121(1): 443-457, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31231887

RESUMO

Accumulating findings reveal that long noncoding RNAs (lncRNAs) as crucial regulatory molecules serve vital functions in the progression of hepatocellular carcinoma (HCC). This study aims to investigate the biological roles and mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in HCC cells based on transcriptome analysis. The Cancer Genome Atlas data analysis and experimental validation showed that HOXD-AS1 was increased in HCC tissues/cell lines and positively relevant to histologic grade. The subcellular localization results indicated HOXD-AS1 was dispersed both in the nucleus as well as the cytoplasm of HCC cells. In vitro loss-of-function experiments revealed that silencing of HOXD-AS1 could dramatically suppress the proliferation, migration, and invasion, and induce S or/and G2/M phase cell cycle arrest as well as apoptosis of Bel-7402 and MHCC97H cells accompanying the changes in expression levels of cyclin B1, cyclin D1, BCL-2, BAX, and MMP2. In vivo assay also showed that HOXD-AS1 silencing could markedly reduce xenograft tumor volume and weight of HCC cells. Transcriptome and bioinformatic analysis indicated that a total of 1103 genes were significantly altered by HOXD-AS1 silencing, of which 132 genes exhibited a significant correlation with HOXD-AS1 expression in HCC tissues. Gene Ontology (GO) enrichment analysis revealed differentially expressed genes were remarkably enriched in several cancer-related biological processes (cell proliferation, cell cycle, apoptosis, migration, angiogenesis, and hypoxic response). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that HOXD-AS1 has the potential to affect p53, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK) pathway, and Western blot results further validated that HOXD-AS1 silencing could inhibit the MEK/ERK pathway in Bel-7402 cells. Collectively, HOXD-AS1, as an oncogenic lncRNA, might exert crucial functions in HCC progression and serve as a potential diagnostic biomarker and therapeutic target for HCC.

2.
Autophagy ; : 1-15, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711362

RESUMO

BAG2 (BCL2 associated athanogene 2) is associated with cell fate determination in response to various pathological conditions. However, the effects of BAG2 on M. tuberculosis-induced endoplasmic reticulum (ER) stress remain elusive. Herein, we report that M. tuberculosis infection of macrophages triggered ER stress and downregulated BAG2 expression. Overexpression of BAG2 enhanced autophagic flux and activated macroautophagy/autophagy targeted to the ER (reticulophagy). In addition, through increasingly localizing SQSTM1 to the ER in BAG2-overexpressing macrophages, we found that the autophagy receptor protein SQSTM1/p62 (sequestosome 1) is associated with the BAG2-induced reticulophagy. Our data also confirmed that BAG2 could render cells resistant to M. tuberculosis-induced cellular damage, and the anti-apoptotic effects of BAG2 in M. tuberculosis-treated macrophages were partially abolished by the autophagic flux inhibitor bafilomycin A1. Furthermore, the dissociation of BECN1 and BCL2 mediated by activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) was responsible for BAG2-activated autophagy. In addition, XBP1 downstream of the ERN1/IRE1 signaling pathway was bound to the Bag2 promoter region and transcriptionally inhibited BAG2 expression. Collectively, these results indicated that BAG2 has anti-apoptotic effects on M. tuberculosis-induced ER stress, which is dependent on the promotion of autophagic flux and the induction of selective autophagy. We revealed a potential host defense mechanism that links BAG2 to ER stress and autophagy during M. tuberculosis infection.Abbreviations: ATF6: activating transcription factor 6; BECN1: beclin 1; Baf A1: bafilomycin A1; CASP3: caspase 3; DDIT3/CHOP/GADD153: DNA damage inducible transcript 3; DAPI: 4',6-diamidino-2-phenylindole; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; HSPA5/GRP78/BiP: heat shock protein 5; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPK/ERK: mitogen-activated protein kinase; SQSTM1/p62: sequestosome 1; UPR: unfolded protein response; XBP1: x-box binding protein 1.

3.
ChemSusChem ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714031

RESUMO

The aerobic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA), a promising renewable polymer monomer to produce bio-based plastics such as polyethylene furanoate (PEF), has emerged as the subject of increasing interest recently. Here, holey 2D Mn2O3 nanoflakes have been obtained via a facile thermal treatment of a Mn-MOF precursor. The structural and morphological properties of the nanoflakes were characterized by PXRD, FTIR, SEM and TEM to explore the formation process. It was inferred that the linker loss in MOF precursor and the oxidation of manganese cation induced by the heat-treatment in air were responsible for the formation of holey 2D Mn2O3 nanoflakes. The specific morphology and redox cycle of manganese cation on the surface endowed the synthesized nanoflakes with promising performance on the selective oxidation. The obtained nanoflakes calcined at 400°C (M400) afforded over 99.5% yield of FDCA at complete conversion of HMF, which was much superior to the catalytic activity of commercial Mn2O3 and activated MnO2. To the best of our knowledge, it is a new record that Mn2O3 could exhibit such a high performance on the aerobic oxidation of HMF to FDCA. Based on the investigation of experiment parameters, a plausible reaction mechanism has been proposed.

4.
Cancer ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714592

RESUMO

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

5.
J Cell Biochem ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696964

RESUMO

The proliferation of hepatic progenitor cells (HPCs) is observed in reactive conditions of the liver and primary liver cancers. Ring1 as a member of polycomb-group proteins which play vital roles in carcinogenesis and stem cell self-renewal was increased in HCC patients and promoted proliferation and survival of cancer cell by degrading p53. However, the mechanisms of Ring1 driving the progression of hepatocarcinogenesis have not been elucidated. In this study, forced expression Ring1 and Ring1 siRNA lentiviral vectors were utilized to stably overexpression and silence Ring1 in HPC cell line (WB-F344), respectively. Our finding indicated that overexpression of Ring1 in HPCs promoted colony formation, cell multiplication, and invasion in vitro, conversely depletion of Ring1 repressed the biological functions of HPCs relative to controls. The expression of ß-catenin was upregulated in the HPCs with overexpression of Ring1, and the correlation analysis also showed that ß-catenin and Ring1 had a significant correlation in the liver cancer tissues and adjacent tissues. The activation of the Wnt/ß-catenin signaling pathway significantly increased the expression of liver cancer stem cells related (LCSCs)-related molecular markers CD90 and EpCAM, which led to the transformation of HPCs into LCSCs. Most importantly, the injection of HPCs with overexpressed Ring1 into the subcutaneous of nude mice leads to the formation of poorly differentiated HCC neoplasm. Our findings elucidate that overexpression of Ring1 the activated Wnt/ß-catenin signaling pathway and drove the transformation of HPCs into cancer stem cell-like cells, suggesting Ring1 has extraordinary potential in early diagnosis of HCC.

6.
Inorg Chem ; 58(22): 15344-15353, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31697488

RESUMO

Internal polarized electric field is found to be an effective and available strategy to separate photogenerated electron-hole pairs. By this method, the efficiency of photocatalytic reactions can be obviously enhanced. Here, the layered compound of BiOIO3 with spontaneous polarization was synthesized by a simple hydrothermal method. Taking another bismuth compound BiOI as a counterpart, which has a similar layered structure, the spontaneous polarization effects of BiOIO3 were analyzed and confirmed. The photocatalytic activity of BiOIO3 and BiOI were evaluated by the degradation of methyl orange. Methyl orange was almost completely photocatalytically decomposed by BiOIO3 and BiOI in 40 and 90 min, respectively. The separation and transfer behaviors of photogenerated electron-hole pairs were investigated by a series of photoelectrochemical characterizations. It is further proved the separation and transmission efficiency of BiOIO3 are higher than those of BiOI. According to the results of density of theory calculations, the internal polarized electric field in BiOIO3 is ascribed to the spatial asymmetry of the IO3 group, which is estimated to ∼1.5 × 1010 V/m. Under the action of this internal polarized electric field, the photogenerated electrons and holes would transfer along opposite directions, i.e., photogenerated electrons and holes respectively gather at the Bi/I side and O side. Additionally, superoxide radicals (•O2-) and holes (h+) are produced during the degradation process, which are responsible for the high visible-light photocatalytic activity. Finally, the cyclic degradation test proves that its photocatalytic performance has long-term stability. Therefore, BiOIO3 polar material can be used as one of the alternative materials for efficient photocatalytic reaction.

9.
Behav Brain Res ; : 112320, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31669345

RESUMO

There is a serious need for fast-acting drugs to treat post-traumatic stress disorder (PTSD). Our previous studies revealed that YL-IPA08, a novel small-molecule TSPO agonist, exerted significant anti-PTSD effects in various animal models. However, the onset time of YL-IPA08 and its underlying mechanisms remain unclear. In the present study, we first investigated the time course of YL-IPA08 compared to selective serotonin reuptake inhibitors (SSRIs) in the well-known time-dependent sensitization model of PTSD. YL-IPA08 required only 2-4 days of treatment to take effect in behavioural models of PTSD, whereas sertraline required 7-8 days. Furthermore, the mechanism study revealed that YL-IPA08 elicited anti-PTSD-like effects associated with increased GABA levels and allopregnanolone efflux in the hippocampus and prefrontal cortex and increased corticosterone levels in the serum after only 5 days of treatment, whereas sertraline required 9 days. Our results demonstrate that YL-IPA08 can exert fast-onset anti-PTSD-like effects, and its mechanisms may be related to the increased GABA levels, allopregnanolone efflux and the hypothalamic-pituitary-adrenal (HPA) axis function.

10.
Mikrochim Acta ; 186(12): 791, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734753

RESUMO

Red-emissive carbon dots (CDs) were synthesized by one-step hydrothermal technique using citric acid (CA), and urea in N,N-dimethylformamide (DMF) solution. The CDs has an average diameter of 2.3 nm, excitation/emission maxima at 553/606 nm, and a low photoluminescence quantum yield (4%). Fluorescence is weakly quenched by the ions Fe3+, Hg2+, Cu2+, Co2+, Zn2+, Ca2+, Ni2+, and Pb2+. After addition of cetyltrimethyl ammonium ion (CTAB), electrostatic interaction between negatively charged CDs and CTAB causes the CDs to self-aggregate. The formation of CD/CTAB increases the average particle diameter to around 13 nm and enhances the quantum yield to 24%. The hydrophobic segments of CTAB twined into a network structure can selectively trap Fe3+ and then interact with surface groups of the CDs to cause quenching. The CD/CTAB nanoprobe enables fluorometric determination of Fe3+ with a linear response in the 0.10-10 µM concentration range and a 0.03 µM limit of detection. The probe was utilized for determination of Fe3+ in human serum samples, and satisfactory results were obtained. Graphical abstractSchematic representation of fluorometric analysis of Fe(III) ion by cetyltrimethyl ammonium ion (CTAB) mediated red emission carbon dots (CDs). The hydrophobic segments of CTAB twined into a network structure can selectively trap Fe(III) and then interact with surface groups of the CDs to cause quenching.

11.
J Cell Biochem ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680309

RESUMO

Dysregulation of long noncoding RNAs (lncRNAs) has been found in a large number of human cancers, including colon cancer. Therefore, the implementation of potential lncRNAs biomarkers with prognostic prediction value are very much essential. GSE39582 data set was downloaded from database of Gene Expression Omnibus. Re-annotation analysis of lncRNA expression profiles was performed by NetAffx annotation files. Univariate and multivariate Cox proportional analyses helped select prognostic lncRNAs. Algorithm of random survival forest-variable hunting (RSF-VH) together with stepwise multivariate Cox proportional analysis were performed to establish lncRNA signature. The log-rank test was carried out to analyze and compare the Kaplan-Meier survival curves of patients' overall survival (OS). Receiver operating characteristic (ROC) analysis was used for comparing the survival prediction regarding its specificity and sensitivity based on lncRNA risk score, followed by calculating the values of area under the curve (AUC). The single-sample GSEA (ssGSEA) analysis was used to describe biological functions associated with this signature. Finally, to determine the robustness of this model, we used the validation sets including GSE17536 and The Cancer Genome Atlas data set. After re-annotation analysis of lncRNAs, a total of 14 lncRNA probes were obtained by univariate and multivariate Cox proportional analysis. Then, the RSF-VH algorithm and stepwise multivariate Cox analysis helped to build a five-lncRNA prognostic signature for colon cancer. The patients in group with high risk showed an obviously shorter survival time compared with patients in group with low risk with AUC of 0.75. In addition, the five-lncRNA signature can be used to independently predict the survival of patients with colon cancer. The ssGSEA analysis revealed that pathways such as extracellular matrix-receptor interaction was activated with an increase in risk score. These findings determined the strong power of prognostic prediction value of this five-lncRNA signature for colon cancer.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31741274

RESUMO

The indoor air quality issue and its potential health problems are attracting increasingly attentions. In this study, micro-orifice uniform deposit impactor (MOUDI) was used to sample suspended particles from four typical indoor environments, including residence, office, cyber classroom, and chemical analysis room. Size-dependent concentrations of perfluoroalkyl substances (PFASs) and heavy metals in suspended particles were analyzed. Then, the International Commission on Radiological Protection deposition model was employed to estimate deposition efficiencies and fluxes of size-fractioned PFASs and heavy metals in the human respiratory tract. Most of the contaminants deposited in head airways, where coarse particles (aerodynamic diameter or Dp > 1.8 µm) contributed the most. By contrast, in the alveolar region fine particles (Dp < 1.8 µm) were dominant. The chronic daily intake through inhalation of PFASs and heavy metals via airborne particles were 10.3-37.5 pg kg-1days-1 and 3.1-25.9 mg kg-1days-1, respectively. The estimated total hazardous quotient of PFASs and heavy metals were 4.4 × 10-5-1.7 × 10-3 and 9.9 × 10-3-1.05 × 10-1, which is far lower than the acceptable threshold of 1. However, the incremental lifetime cancer risk induced by As, Cd, Co, Cr, and Ni were estimated to be 1.11 × 10-5-1.41 × 10-4 in total, which exceeded the acceptable threshold of 10-6. These findings implicate that there were health risks, especially cancer risks caused by heavy metals associated with airborne particles in urban indoor environments.

14.
Pediatrics ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732547

RESUMO

BACKGROUND: Coronary artery aneurysms (CAAs) are a well-known complication of Kawasaki disease (KD), but there are no data on incidence or outcomes of systemic artery aneurysms (SAAs) in the current era. METHODS: From April 1, 2016, to March 31, 2019, we screened for SAAs in 162 patients with KD at risk for SAAs with magnetic resonance angiography or peripheral angiography and analyzed incidence and early outcomes of SAAs. RESULTS: Twenty-three patients had SAAs, demonstrating an incidence of 14.2% (23 of 162) in patients who were screened at 1 month after onset. The proportion of patients with SAAs was estimated to be 2% (23 of 1148) of all patients with KD. The median age at onset of KD with SAAs was 5 months. All patients with SAAs had CAAs, with z scores >8. Of patients with giant CAAs, 38.6% (17 of 44) had SAAs. A total of 129 SAAs occurred in 17 different named arteries. The most common sites for SAAs were the axillary (18.6%), common iliac (12.4%), and brachial (11.6%) arteries. During a median follow-up time of 6 months, 92.9% (79 of 85) of SAAs had some degree of regression, with 80% (68 of 85) of SAAs returning to normal. The overall regression rate was higher for medium to large SAAs than for medium to giant CAAs. CONCLUSIONS: Although the incidence of SAAs may not be as dramatically reduced as we expected compared with previous data, SAAs have a high regression rate during short-term follow-up.

15.
J Asian Nat Prod Res ; : 1-10, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738086

RESUMO

Filoviruses cause severe hemorrhagic fever in humans. Ebola virus (EBOV) is the most contagious filovirus. Although compassionate treatments have been used during the latest Ebola outbreak, novel anti-EBOV agents are still urgently needed. In this study, sclareol and sclareolide, two natural products in Salvia sclarea, were identified as EBOV entry inhibitors with EC50s of 2.4 µmol/L and 8.0 µmol/L, respectively, through blocking the viral fusion process. Moreover, both compounds exhibited inhibitory effects on all tested filoviruses' entry, indicating their wide-spectrum activities against filoviruses. This study provides insights into the two natural products and their applications against filovirus infectious diseases.

16.
Sci Rep ; 9(1): 16172, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31700086

RESUMO

Phellinus baumii, also called "Sang Huang" in China, is broadly used as a kind of health food or folk medicine in Asia for its high biological activities, e.g. anti-tumor, anti-oxidation and anti-inflammatory activities. Although some previous studies have indicated that polysaccharides and flavonoids showed the activity of inhibiting tumor cells, the active metabolites of P. baumii needs further research. In our study, a stable P. baumii mutant (A67), generated by ARTP mutagenesis strategy, showed more significantly inhibiting tumor cells and enhancing antioxidant activity. Our further studies found that the increase of polyphenols content, especially hispidin, was an important reason of the biological activity enhancement of A67. According to the results of the integrated metabolome and proteome study, the increase of polyphenol content was caused by upregulation of the phenylpropanoid biosynthesis. This study expanded the understanding of active compounds and metabolic pathway of P. baumii.

17.
Eur J Med Chem ; : 111900, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31771827

RESUMO

Since dual inhibitors may yield lower toxicity and reduce the likelihood of drug resistance, as well as inhibitors of HIV-1 PR and RT constitute the core of chemotherapy for AIDS treatment, we herein designed and synthesized new coumarin derivatives characterized by various linkers that exhibited excellent potency against PR and a weak inhibition of RT. Among which, compounds 6f and 7c inhibited PR with IC50 values of 15.5 and 62.1 nM, respectively, and weakly affected also RT with IC50 values of 241.8 and 188.7 µM, respectively, showing the possibility in the future of developing dual HIV-1 PR/RT inhibitors. Creative stimulation for further research of more potent dual HIV-1 inhibitors was got according to the molecular docking studies.

18.
J Hazard Mater ; : 121688, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31776082

RESUMO

Perfluorooctanoic acid (PFOA) from contaminated soil accumulates in higher organisms, and causes health risks to humans. In this research, 71 % of the PFOA was degraded, of which 51 % was decomposed into short chain by-products, 19 % mineralized, and 1 % volatilized with 30 kV of voltage, 50 Hz of discharge frequency, 1 % of soil moisture, 300 ppm of PFOA concentration and 6.3 of soil pH using pulsed positive discharge plasma. From a series of experiments, electrons were identified as the dominant active means of PFOA degradation. The decomposition by-products were analyzed by LC-MS. The results indicated that PFOA was decomposed into small by-products including perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluoropentanoic acid (PFPeA), perfluorobutyric acid (PFBA), pentafluoropropionic acid (PFPrA) and trifluoroacetic acid (TFA). Moreover, in plasma treated soil, the concentration of ammonia nitrogen increased from less than 10 ppm-462 ppm, and the average dry weight of lettuce was 1.6 mg higher than that in natural soil. Additionally, Planctomycetes and Nitrospirae increased after treatment, indicating that plasma technology promotes the process of nitrogen cycle. Thus, PFOA polluted soil could be remediated using this pulse corona plasma technology, and simultaneously improve the fertility of soil without chemical injections.

19.
J Am Chem Soc ; 141(44): 17875-17883, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31603671

RESUMO

Pyridinium has been shown to be a cocatalyst for the electrochemical reduction of CO2 on metal and semiconductor electrodes, but its exact role has been difficult to elucidate. In this work, we create cooperative cobalt-protoporphyrin (CoPP) and pyridine/pyridinium (py/pyH+) catalytic sites on metal-organic layers (MOLs) for an electrocatalytic CO2 reduction reaction (CO2RR). Constructed from [Hf6(µ3-O)4(µ3-OH)4(HCO2)6] secondary building units (SBUs) and terpyridine-based tricarboxylate ligands, the MOL was postsynthetically functionalized with CoPP via carboxylate exchange with formate capping groups. The CoPP group and the pyridinium (pyH+) moiety on the MOL coactivate CO2 by forming the [pyH+--O2C-CoPP] adduct, which enhances the CO2RR and suppresses hydrogen evolution to afford a high CO/H2 selectivity of 11.8. Cooperative stabilization of the [pyH+--O2C-CoPP] intermediate led to a catalytic current density of 1314 mA/mgCo for CO production at -0.86 VRHE, which corresponds to a turnover frequency of 0.4 s-1.

20.
Can J Diabetes ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31594761

RESUMO

OBJECTIVES: MicroRNAs have been reported to participate in various important cell biological processes, such as glucose metabolism. The aim of this study was to explore the roles of microRNA-15a (miR-15a) in regulating insulin sensitivity. METHODS: In L6 rat skeletal muscle cells, we observed the effect of miR-15a on glucose metabolism and glucose transporter 4 (GLUT4) translocation by targeting vesicle-associated membrane protein-associated protein A (VAP-A) after insulin treatment. Luciferase reporter assays were performed to demonstrate a direct interaction between miR-15a and the 3'-untranslated region of VAP-A microRNA. RESULTS: We identified miR-15a as an extremely important regulator of GLUT4 translocation via targeting of VAP-A. Additionally, knockdown of endogenous miR-15a or overexpression of VAP-A could increase extracellular glucose by inhibiting the translocation of GLUT4 to the cell membrane after insulin treatment. However, overexpression of miR-15a or knockdown of VAP-A had no significant effect on glucose metabolism. CONCLUSIONS: These findings reveal the following: 1) VAP-A is a marker of skeletal muscle glucose disposal and 2) a novel mechanism for GLUT4 translocation by miR-15a.

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