RESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the gastrointestinal malignancies with high prevalence and poor prognosis. Previous reports suggested that circular ribose nucleic acids might exert regulatory functions in ESCC. This study aims to explore the role of circ_0000592 in ESCC progression, providing novel insights into the diagnosis and therapeutic avenues for ESCC. The GSE131969 data set was utilized to assess circ_0000592 expression in ESCC. The validation was performed in the tumorous tissues of ESCC patients (n = 80) and human-immortalized ESCC cell lines. The correlation between circ_0000592 expression and prognosis was analyzed. The impact of circ_0000592 on ESCC cell activity was evaluated through downregulating circ_0000592, as well as encompassing cell viability, migration, and invasion abilities. The downstream pathway of circ_0000592 was explored by binding site prediction from the TargetScan database, followed by in vitro and in vivo experiments. An in vivo xenograft tumor model was established to highlight the role of circ_0000592 in ESCC. Patients with ESCC exhibited higher circ_0000592 expression levels compared to noncancerous patients, which were associated with reduced survival time, higher TNM stage, and increased lymph node metastasis. The circ_0000592 downregulation suppressed cell viability, migration, and invasion abilities in vitro. Mechanistically, circ_0000592 countered the inhibitory effects on the target gene Frizzled 5 (FZD5) through interactions with miR-155-5p. The overexpression of miR-155-5p curtailed the luciferase activity of circ_0000592 in ESCC cells, inhibiting downstream molecule FZD5 protein expression and subsequently mitigating the detrimental consequences of escalated circ_0000592 expression in ESCC cells. Consistently, circ_0000592 downregulation curbed proliferation and metastasis of ESCC tumors in vivo. In summary, circ_0000592 promoted the progress of ESCC by counteracting the inhibitory impact on FZD5 through its interaction with miR-155-5p. Together, our findings highlighted circ_0000592 as a prospective therapeutic target for ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Receptores Frizzled , MicroRNAs , RNA Circular , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Receptores Frizzled/metabolismo , Receptores Frizzled/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismoRESUMO
The tumor suppressor LKB1 gene encodes a serine-threonine kinase that regulates cell proliferation and polarity. Inactivation of LKB1 by mutations in LKB1 or loss of its expression is highly correlated with lung, ovarian, and pancreatic cancers, and WNT/ß-catenin pathway is also known to be involved in many human malignancies. However, the relationship between LKB1 and WNT signaling pathway in esophageal carcinoma remains unknown. The expression of LKB1 in 62 cases of esophageal cancer patients was determined by quantitative real-time PCR. It was found that LKB1 mRNA level was significantly lower than the adjacent normal epithelium and that the LKB1 downregulation was correlating with TNM stages. Moreover, the expression of WNT target genes such as Cyclin D1, C-MYC, MMP2, and FZD2 was significantly upregulated in esophageal cancer tissues. LKB1 overexpression in TE10 cells inhibited TOPFlash luciferase reporter activity and WNT target gene expression even in the presence of WNT3A. Conversely, LKB1 knockdown enhanced WNT signaling activity in esophageal cancer cells. It was also found that LKB1 antagonized WNT signaling pathway through interaction with GSK3ß to downregulate ß-catenin expression level. Functional investigation revealed that LKB1 suppressed the promotion effects of WNT3A on the cell growth of TE10 cells. The LKB1 functions in regulating cell growth and WNT target genes expression were impaired by GSK3ß inhibition, suggesting that LKB1 antagonized WNT-induced cell proliferation through enhancement of GSK3ß activity. Together, the interaction between LKB1 and GSK3ß upregulates GSK3ß activity to suppress WNT-induced cell proliferation in esophageal carcinoma cells. Loss of LKB1 expression may result in the deregulation of WNT/ß-catenin pathway to promote malignant progression of esophageal cancer.
Assuntos
Neoplasias Esofágicas/genética , Quinase 3 da Glicogênio Sintase/genética , Proteínas Serina-Treonina Quinases/metabolismo , Via de Sinalização Wnt/genética , Quinases Proteína-Quinases Ativadas por AMP , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Quinase 3 da Glicogênio Sintase/biossíntese , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/biossíntese , beta Catenina/biossíntese , beta Catenina/metabolismoRESUMO
NAD(P)H: quinone oxidoreductase 1 (NQO1) is an important enzyme which can catalyze the two-electron reduction of quinoid compounds into hydroquinones. NQO1 Pro187Ser polymorphism can change the enzymatic activity of NQO1, and it has been proposed to be associated with risk of esophageal cancer. We performed a meta-analysis to examine the association between NQO1 Pro187Ser polymorphism and esophageal cancer. Odds ratio (OR) with a 95% confidence interval (95% CI) was used to assess the association. Twelve case-control studies with 1,725 cases with esophageal cancer and 2,341 controls were finally included in the meta-analysis. Overall, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer (allele model: OR = 1.24, 95% CI 1.06-1.46, P OR = 0.009; homozygote model: OR = 1.59, 1195% CI 1.10-2.30, P OR = 0.013; dominant model: OR = 1.31, 95% CI 1.05-1.64, P OR = 0.018). In the subgroup analysis by ethnicity, there was an obvious association between NQO1 Pro187Ser polymorphism and esophageal cancer in Asians but not in Caucasians. Therefore, the meta-analysis suggests that NQO1 Pro187Ser polymorphism is associated with esophageal cancer risk.
Assuntos
Neoplasias Esofágicas/genética , Predisposição Genética para Doença/genética , NAD(P)H Desidrogenase (Quinona)/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética , Estudos de Casos e Controles , Humanos , Razão de Chances , População Branca/genéticaRESUMO
OBJECTIVE: The objective of this study is to assess the use of a novel, double-lumen electrocautery tube (DLET) device for ablating the sympathetic nerve chain in patients with primary palmar hyperhidrosis (PPH). METHODS: Forty-six patients with severe PPH were recruited into the study between November 2010 and February 2012. All patients underwent single port, bilateral video-assisted thoracoscopic sympathicotomy. Twenty-four patients were randomized to receive sympathicotomy using a conventional 5-mm electrocautery hook (hook group) and 22 patients were randomized to the DLET group. RESULTS: The mean postoperative follow-up period was 8.1 months (range: 1 to 15 months). After surgery the hands of all patients became dry and warm. Mean incision size was 10.6 ± 1.0 in the hook group and 6.5 ± 0.5 mm in the DLET group (p = 0.001). The mean pain score was 1.4 ± 0.6 with hook surgery and 0.9 ± 0.6 with the DLET device (p = 0.016). The mean operative time was longer in the hook group (36.8 ± 3.4 min) than in the DLET group (30.5 ± 3.9 min; p = 0.001). There were no significant differences between the two procedures in terms of hospital stay and compensatory sweating, or patient satisfaction. Pneumothorax occurred in two (8.3%) patients in the hook group and in one (4.5%) patient in the DLET group. None of the patients required chest drainage and none developed Horner syndrome. CONCLUSIONS: Single-port video-assisted thoracoscopic sympathicotomy using hook or DLET procedures is effective, safe, and minimally invasive method for palmar hyperhidrosis. The DLET device allows a shorter operation time, smaller incision, better cosmetic results, less pain, and better clarity of video, making it suitable for single-port thoracoscopic sympathicotomy.
Assuntos
Hiperidrose/cirurgia , Simpatectomia/instrumentação , Sistema Nervoso Simpático/cirurgia , Cirurgia Torácica Vídeoassistida/instrumentação , Adolescente , Adulto , Eletrocoagulação/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background: Circular RNAs (circRNAs) are crucial regulators in human cancers, including non-small cell lung cancer (NSCLC). In this study, we explore the biological functions and molecular mechanisms of circ_0074027 in NSCLC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ_0074027, paired like homeodomain 1 (PITX1) mRNA, microRNA-335-5p (miR-335-5p), and cullin 4B (CUL4B) mRNA. The features of circ_0074027 were analyzed by RNase R digestion assay. Flow cytometry analysis was adopted to analyze cell cycle and cell apoptosis. Cell counting kit-8 (CCK-8) assay and colony formation assay were performed to assess cell proliferation. Western blot assay was conducted to measure protein levels. Dual-luciferase reporter and RNA pull-down assays were carried out to verify the relationships among circ_0074027, miR-335-5p, and CUL4B. The murine xenograft model was established to investigate the role of circ_0074027 in vivo. Results: High expression of circ_0074027 was found in NSCLC tissues and cells. Circ_0074027 knockdown suppressed cell viability, cell cycle process, and colony formation and promoted apoptosis in NSCLC cells in vitro and inhibited tumor growth in vivo. Circ_0074027 acted as a sponge of miR-335-5p. The effect of circ_0074027 knockdown on NSCLC progression was weakened by miR-335-5p inhibition. Moreover, CUL4B was a target gene of miR-335-5p. CUL4B overexpression reversed the inhibitory effects on cell viability, cell cycle process, and colony formation and the promotional effect on cell apoptosis caused by miR-335-5p in NSCLC. Conclusion: Circ_0074027 facilitated NSCLC cell progression through regulating miR-335-5p/CUL4B axis.