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OBJECTIVE: Accumulating evidence reveals that aberrant expression of microRNAs contributes to the tumorigenesis and development of diverse human cancers. In the current study, we aimed to evaluate the functional role and prognostic value of miR-149-3p in oral squamous cell carcinoma (OSCC). METHODS: Real-time polymerase chain reaction (PCR) analysis was performed to detect the expression of miR-149-3p in 70 OSCC patients (64.10 ± 11.97 years; 31 males and 39 females). The prognostic ability of miR-149-3p in OSCC patients was assessed by Kaplan-Meier survival analysis. Transwell assays and cell adhesion assays were used to investigate the impact of miR-149-3p on cell migration and invasion. The regulation of MMP2 expression by miR-149-3p was determined by real-time PCR, western blotting and dual luciferase reporter assay. RESULTS: Our results revealed a lower level of miR-149-3p in OSCC tissues than in adjacent normal tissues. Downregulation of miR-149-3p was correlated with malignant development and poor outcomes in patients with OSCC. MiR-149-3p repressed the migratory and invasive abilities of OSCC cells. We confirmed that miR-149-3p targeted the 3'-untranslated region of MMP2 mRNA to suppress MMP2 expression. Moreover, the miR-149-3p-mediated decrease in metastasis was reversed by overexpression of MMP2 in OSCC cells. CONCLUSION: Our findings provide an important molecular mechanism by which miR-149-3p inhibits OSCC cell migration and invasion via negative regulation of MMP2 and implicate miR-149-3p as a prospective biomarker and therapeutic target for OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , MicroARNs , Neoplasias de la Boca , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Neoplasias de la Boca/genética , Pronóstico , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
MicroRNAs (miRs) exhibit oncogenic or tumor suppressive functions that contribute to the initiation and development of various types of human cancer. miR1493p has been reported to serve multiple roles in the regulation of proliferation, apoptosis and metastasis. However, the effects and detailed mechanism of miR1493p in oral squamous cell carcinoma (OSCC) remain unclear. In the present study, miR1493p mimic, mimic control, miR1493p inhibitor and inhibitor control were transiently transfected into Cal27 and SCC9 cells. The viability, proliferation and apoptosis of OSCC cells were determined using Cell Counting Kit8, colony formation and Annexin V assays, respectively. The mRNA expression levels of miR1493p and AKT2 were determined by reverse transcriptionquantitative PCR. The protein expression levels of AKT2, cleaved caspase3 and cleaved PARP were examined by western blot analysis. The binding of miR1493p to the AKT2 3'untranslated region was evaluated by a dual luciferase reporter assay. In the present study, overexpression of miR1493p reduced the viability and proliferation of OSCC cells. By contrast, increased cell viability and proliferation was observed in miR1493pdeficient OSCC cells. Dual luciferase reporter assay indicated that miR1493p significantly decreased the luciferase activity of the wildtype AKT2 3'untranslated region. Moreover, overexpression of miR1493p downregulated the mRNA and protein expression levels of AKT2, suggesting that miR1493p was a negative modulator of AKT2. Restoration of AKT2 efficiently reversed the miR1493pmediated reduction in the proliferative capacity of OSCC cells. In addition, miR1493p enhanced the sensitivity of OSCC cells to the chemotherapeutic drug 5fluorouracil. Taken together, the current findings revealed an inhibitory effect of miR1493p on the proliferation of OSCC cells through the posttranscriptional suppression of AKT2, and indicated a potential chemosensitizing function of miR1493p for the treatment of patients with OSCC.
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Proliferación Celular , Neoplasias de Cabeza y Cuello/metabolismo , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Neoplásico/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Línea Celular Tumoral , Fluorouracilo/farmacología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Neoplásico/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
Following the publication of this article, we realize that the title appeared incorrectly: This appeared in print as "Long noncoding RNA H1 promotes cell proliferation and invasion by acting as a ceRNA of miR138 and releasing EZH2 in oral squamous cell carcinoma", and the corrected title is now featured above ("H1" should have read as "H19"). Note that this error did not have any bearing on the results reported in the paper, or on the conclusions therein. We regret any inconvenience that this mistake has caused. [the original article was published in the International Journal of Oncology 52: 901912, 2018; DOI: 10.3892/ijo.2018.4247].
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Long non-coding RNAs (lncRNAs) have been shown to play pivotal roles in various types of human cancer, including oral squamous cell carcinoma (OSCC). However, the potential mechanisms of action of lncRNAs in OSCC remain to be fully elucidated. The aim of the present study was to further explore the potential mechanisms of action of lncRNAs in OSCC. We first analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly expressed lncRNAs which may be involved in the development of OSCC. Reverse transcriptionquantitative PCR (RTqPCR) was performed to analyze the expression levels of lncRNA H19. In addition, the correlation between H19 expression and the clinical characteristics and prognosis of patients with OSCC was statistically analyzed. The effects of H19 expression on OSCC cells were examined by using overexpression and RNA interference approaches in vitro and in vivo. To examine the competitive endogenous RNA (ceRNA) mechanisms, bioinformatics analysis and luciferase reporter assay were performed. In addition, the correlation between H19 and microRNA (miR)138 was detected. H19 was found to be upregulated in OSCC tissues and its high expression level was associated with the TNM stage and nodal invasion, and also correlated with a shorter overall survival of patients with OSCC. The knockdown of H19 significantly inhibited OSCC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and induced apoptosis in vitro; it also suppressed subcutaneous tumor growth in vivo. In addition, H19 was found to regulate the expression of oncogene enhancer of zeste homolog 2 (EZH2) by competing with miR138; the inhibition of miR138 attenuated the inhibitory effects of H19 knockdown on OSCC cells. On the whole, our findings suggest that H19 functions as an oncogene by inhibiting miR138 and facilitating EZH2 expression in OSCC. Thus, lncRNA H1 may represent a potential therapeutic target for OSCC.
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Carcinoma de Células Escamosas/genética , Proteína Potenciadora del Homólogo Zeste 2/genética , MicroARNs/genética , Neoplasias de la Boca/genética , ARN Largo no Codificante/metabolismo , Animales , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Femenino , Perfilación de la Expresión Génica/métodos , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Invasividad Neoplásica/genética , Estadificación de Neoplasias , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Análisis de Supervivencia , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The thermoelectric (TE) performance of films of colloidal lead selenide (PbSe) quantum dots (QDs) with metal-chalcogenide complex ligands is seen to change with QD size and temperature. Films of smaller QDs have higher Seebeck coefficient magnitudes, indicating stronger quantum confinement, and lower electrical and thermal conductivities. The thermoelectric figure of merit ZT is â¼0.5 at room temperature and increases with temperature to 1.0-1.37 at â¼400 K, where it is larger for smaller QD films. This is better than previous results for solution-prepared QD TE materials at these elevated temperatures.
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An HPLC method was developed and validated to compare the chemical profiles and tyrosinase inhibitors in the woods, twigs, roots, and leaves of Artocarpus heterophyllus . Five active tyrosinase inhibitors including dihydromorin, steppogenin, norartocarpetin, artocarpanone, and artocarpesin were used as marker compounds in this HPLC method. It was discovered that the chemical profiles of A. heterophyllus twigs and woods are quite different. Systematic chromatographic methods were further applied to purify the chemicals in the twigs of A. heterophyllus. Four new phenolic compounds, including one isoprenylated 2-arylbenzofuran derivative, artoheterophyllin A (1), and three isoprenylated flavonoids, artoheterophyllin B (2), artoheterophyllin C (3), and artoheterophyllin D (4), together with 16 known compounds, were isolated from the ethanol extract of the twigs of A. heterophyllus. The structures of compounds 1-4 were elucidated by spectroscopic analysis. However, the four new compounds did not show significant inhibitory activities against mushroom tyrosinase compared to kojic acid. It was found that similar compounds, such as norartocarpetin and artocarpesin in the twigs and woods of A. heterophyllus, contributed to their tyrosinase inhibitory activity.
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Artocarpus/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Péptidos/química , Extractos Vegetales/química , Agaricales/enzimología , Proteínas Fúngicas/antagonistas & inhibidores , Corteza de la Planta/química , Raíces de Plantas/químicaRESUMEN
BACKGROUND: The number of blood vessels correlates with metastasis in solid tumors, including oral squamous cell carcinoma (OSCC). Hypoxia inducible factor-1alpha (HIF-1alpha) could play a role in tumor lymphangiogenesis by regulating the lymphatic expression of vascular endothelial growth factor-C (VEGF-C). HIF-1alpha protein expression, VEGF-C protein expression, lymphatic vessel density (LVD) and blood vessel density (BVD) in OSCC were investigated. MATERIALS AND METHODS: HIF-1alpha and VEGF-C protein expression were investigated by means of immunohistochemistry in samples from 65 cases of OSCC. The density of the lymphatic microvessels and blood microvessels immunohistochemically stained by LYVE-1 and CD34 antibody, respectively, was calculated. The association between the HIF-1alpha expression and the clinicopathological parameters was evaluated. RESULTS: HIF-1alpha overexpression occurred in 43 out of the 65 tumor samples (66.2%), while VEGF-C overexpression was observed in 34 out of the 65 tumor samples (52.3%). Higher LVD was found in both high HIF-1alpha and high VEGF-C expression cases. HIF-1alpha overexpression was significantly correlated with VEGF-C overexpression (p = .018, Chi-square test), higher LVD (p < 0.001, Mann-Whitney U-test), and regional lymph nodal involvement (p = 0.004, Chi-square test) as well as UICC TMN classification (p = 0.043, Chi-square test), respectively. In addition, higher BVD existed in the high HIF-1alpha and VEGF-C expression groups (p < 0.001, Mann-Whitney U-test). CONCLUSION: HIF-1alpha might play a crucial role in regional lymph node metastasis as a regulator of lymphangiogenesis and angiogenesis in OSCC with a possible novel pathway involving VEGF-C. Therefore, HIF-1alpha might be a particularly promising target for controlling regional lymph node metastases by a combination of antiangiogenic and anti-lymphangiogenic effects in OSCC.