RESUMEN
Wiskott-Aldrich syndrome protein family verprolin-homologous domain-containing protein 3 (WAVE3) is reported as an oncogene regulating cell proliferation and motility in multiple malignancies, while its role in tongue squamous cell carcinoma (TSCC) remains unknown. This study aimed to explore the expression and mechanism of WAVE3 in TSCC. We enrolled 64 TSCC patients admitted between June 2013 and February 2014 and collected their cancerous and adjacent normal tissues to determine WAVE3 expression by immunohistochemistry. The correlation of WAVE3 expression with TSCC patients' pathological characteristics was analyzed. Then, a 7-year follow-up was conducted to observe the value of WAVE3 in evaluating patient outcomes. In addition, human TSCC SCC9, SCC25, and CAL27 cells were purchased and detected by Cell Counting Kit-8 (CCK-8), Transwell, and scratch-wound assays for their proliferation, invasion, and migration capacities, while real-time quantitative PCR (qRT-PCR) and Western blotting were utilized to quantify WAVE3 and epithelial-mesenchymal transition (EMT)-related protein expression, respectively. The most active cell lines were selected to be infected with lentiviral vectors that silenced WAVE3 (named WAVE3-sh group) and overexpressed WAVE3 cDNA (named WAVE3-OE group) to observe the impacts of interfering WAVE3 expression on TSCC cell biological behavior. The positive expression of WAVE3 in TSCC tissue was found to be obviously enhanced and predominantly located in the cytoplasm. In addition, close correlations were identified between WAVE3 and T staging, clinical staging, lymphatic metastasis, distant metastasis, and differentiation degree (P < 0.05). Increased WAVE3 expression predicted an elevated risk of death, as indicated by the follow-up analysis (P < 0.05). SCC9 was selected for subsequent experiments among various TSCC cell lines studied because it showed the most potent ability to proliferate, invade, and migrate (P < 0.05). Silencing WAVE3 expression in SCC9 cells decreased cell proliferation, invasion, migration, and EMT-related protein expression (P < 0.05), while increasing WAVE3 expression promoted SCC9 viability. WAVE3, which was highly expressed in TSCC, promoted EMT in tumor cells and accelerated their proliferation, invasion, and migration, which might provide a new theoretical basis for molecular targeted therapy of TSCC in the future.
RESUMEN
Tongue squamous cell carcinoma (TSCC) is one of the most common malignant tumors of head and neck. Its incidence is on the rise, and the proportion of young patients is gradually increasing, which is prone to tumor recurrence and metastasis. At present, there is no effective method to completely treat TSCC. Studies have shown that brucea javanica oil (BJO) has good antitumor activity against lung cancer and gastrointestinal tumors, but its therapeutic effect on TSCC is not clear. We have previously confirmed that oleic acid, the main component of BJO, can induce apoptosis of TSCC and reduce its invasion and metastasis ability. However, the anticancer effect and mechanism of BJO in TSCC remain unclear. In order to further explore the effects of BJO on the biological characteristics of TSCC cells, we studied the effects of different concentrations of BJO on the migration, invasion ability and epithelial mesenchymal transition (EMT) progression of TSCC cells and the possible mechanisms through in vitro experiments. We found that BJO could inhibit the invasion and metastasis of TSCC and up-regulate miR-138. After BJO treatment, the expression of E-cad was significantly increased, while the expression of EZH2, Slug, p-ERK1/2 and Vimentin was significantly decreased. EZH2 is a miR-138 target gene involved in TSCC. BJO inhibits TSCC invasion and metastasis by regulating the miR-138-EZH2 pathway. In vivo experiments have also well demonstrated the targeting effect of this pathway. This study provides a new therapeutic strategy for the treatment of TSCC.
Asunto(s)
Carcinoma de Células Escamosas , MicroARNs , Neoplasias de la Lengua , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Brucea javanica , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/metabolismo , Recurrencia Local de Neoplasia , Lengua , Células Epiteliales/metabolismo , Células Epiteliales/patología , MicroARNs/genética , MicroARNs/metabolismo , Proteína Potenciadora del Homólogo Zeste 2RESUMEN
MTFR2 is an oncogene involved in the progression of cancer, its' potential mechanism in oral squamous carcinoma remains unknown. The aim of this study was to uncover the bio-function and the mechanism of MTFR2 in the progression of oral squamous carcinoma. We scanned TCGA database to identify MTFR2 as dysregulated genes. qRT-PCR and Western blotting assays were applied to detect the expression pattern of MTFR2 in oral squamous carcinoma. We next established stable MTFR2-overexpressing and MTFR2 knocking down cell lines. A series of experiments were applied and the results indicated that MTFR2 was upregulated in cancer tissue and negatively correlated with the overall survival (OS) of patients in both the TCGA database and our inhouse database. Following experiments showed that MTFR2 promotes proliferation, migration and invasion in an oral squamous carcinoma cell line by switching OXPHOS to glycolysis.
RESUMEN
Electroacupuncture (EA) has been documented as a form of therapy for chronic sinusitis (CRS). The present study aimed to assess the effects of EA combined with interleukin10 (IL10) overexpression on CRS in mice, and to investigate the associated mechanisms. A mouse model of CRS was established by the administration of ovalbumin (OVA), and overexpression of IL10 was induced using virusencoded IL10. The experimental groups were as follows: i) Control group; ii) OVA group; iii) OVA + EA group; iv) OVA + empty vector group; v) OVA + vector + EA group; vi) OVA + IL10 group; and vii) OVA + IL10 + EA group. Pathological changes and nasal mucus were analyzed using hematoxylin and eosin staining. Interferonγ (IFNγ) and IL10 were detected via reversetranscription quantitative PCR and western blot analyses. The pseudostratified epithelium of the mucosa of the nasal sinus was impaired following the induction of CRS. Treatment with EA and/or IL10 reversed the injury. Combination treatment with EA and IL10 induced synergistic effects. No infiltration of inflammatory cells was observed in the submucosa following EA and IL10 treatment. Compared with the control group, the expression of IFNγ and IL10 in the OVA group was reduced. By contrast, EA or the overexpression of IL10 inhibited this reduction. Furthermore, the combined application of EA and IL10 had a significantly more potent inhibitory effect on the reduction of IFNγ expression, but not IL10. Collectively, EA combined with IL10 induced specific effects on CRS in mice, likely through the upregulation of IFNγ and IL10. The current study presented mechanistic implications for the application of EA as an alternative treatment for CRS.
Asunto(s)
Enfermedad Crónica/terapia , Electroacupuntura/métodos , Pólipos Nasales/terapia , Sinusitis/terapia , Animales , Modelos Animales de Enfermedad , Humanos , Interferón gamma/genética , Interleucina-10/genética , Ratones , Mucosa Nasal/patología , Pólipos Nasales/patología , Sinusitis/genéticaRESUMEN
Oleic acid (OA), a main ingredient of Brucea javanica oil (BJO), is widely known to have anticancer effects in many tumors. In this study, we investigated the anticancer effect of OA and its mechanism in tongue squamous cell carcinoma (TSCC). We found that OA effectively inhibited TSCC cell proliferation in a dose- and time-dependent manner. OA treatment in TSCC significantly induced cell cycle G0/G1 arrest, increased the proportion of apoptotic cells, decreased the expression of CyclinD1 and Bcl-2, and increased the expression of p53 and cleaved caspase-3. OA also obviously induced the formation of autolysosomes and decreased the expression of p62 and the ratio of LC3 I/LC3 II. The expression of p-Akt, p-mTOR, p-S6K, p-4E-BP1 and p-ERK1/2 was significantly decreased in TSCC cells after treatment with OA. Moreover, tumor growth was significantly inhibited after OA treatment in a xenograft mouse model. The above results indicate that OA has a potent anticancer effect in TSCC by inducing apoptosis and autophagy via blocking the Akt/mTOR pathway. Thus, OA is a potential TSCC drug that is worthy of further research and development.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Ácido Oléico/farmacología , Animales , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Previous evidence has indicated an increased cancer risk in individuals with diabetes mellitus (DM). The aim of this study was to investigate the relationship between DM (high glucose) and tongue squamous cell carcinoma (TSCC) and how high glucose mediated the metastatic potential of TSCC. The relationship between DM and TSCC was assessed in a retrospective study. The role and its mechanism of high glucose on the proliferation, metastatic potential of TSCC were investigated in vitro and in vivo. The prevalence rate of DM in patients with TSCC was 12.84%, which was significantly higher than that (9.7%) in the general population in China. Although no significant difference was observed in the overall survival (OS) rate, TSCC patients with DM have a 1.38-fold increase in relative risk affecting 5-year OS compared to patients without DM. High glucose enhanced the TSCC cell proliferation, migration, invasion and upregulated PKM2 (pyruvate kinase M2) expression. Whereas, these effect was abolished after knockdown of PKM2 in TSCC cells. High glucose promoted tumour growth and lung metastasis of TSCC in a DM animal model. Our results confirm DM as a risk factor for the development of TSCC. High glucose enhances the metastatic potential of TSCC through stimulation of the PKM2 pathway.