RESUMO
Tumor-associated macrophages (TAMs) in the tumor microenvironment have been associated with enhanced tumor progression. In this study, we investigated the role and molecular mechanisms of MALAT1 in TAMs derived from thyroid cancer. The expression of MALAT1 and FGF2 in thyroid cancer tissues and cells were measured by quantitative real-time PCR and Western blot. TAMs were transfected with indicated constructs. Then the culture medium (CM) from TAMs was harvested for assay. Secreted FGF2 protein levels and TNF-α, IL-12, and IL-10 levels were detected by ELISA. The cell proliferation, migration, and invasion of FTC133 cells were determined with a CCK-8 assay and a Transwell assay, respectively. In addition, HUVEC vasculature formation was measured by matrigel angiogenesis assay. The higher levels of MALAT-1 and FGF2 were observed in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. Besides, in the presence of si-MALAT1, the levels of TNF-α and IL-12 were significantly up-regulated whereas IL-10 was down-regulated in the CM from TAMs. Moreover, down-regulation of MALAT1 in TAMs reduced proliferation, migration, and invasion of FTC133 cells and inhibited angiogenesis. However, overexpression of FGF2 blocked the effects of MALAT1 siRNAs on cell migration, invasion, and angiogenesis. Our results suggest that MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of FTC133 cells and induces vasculature formation. J. Cell. Biochem. 118: 4821-4830, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Macrófagos/metabolismo , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Idoso , Linhagem Celular Tumoral , Feminino , Fator 2 de Crescimento de Fibroblastos/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Neoplasias da Glândula Tireoide/irrigação sanguínea , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
BACKGROUND: Endoscopic thyroidectomy for minimally invasive thyroid surgery has been widely applied in the past decade. The present study aimed to evaluate the effects of single-port access transaxillary totally endoscopic thyroidectomy on the postoperative outcomes and functional parameters, including quality of life and cosmetic result in patients with papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: Seventy-five patients with PTC who underwent endoscopic thyroidectomy via a single-port access transaxillary approach were included (experimental group). A total of 123 patients with PTC who were subjected to conventional open total thyroidectomy served as the control group. The health-related quality of life and cosmetic and satisfaction outcomes were assessed postoperatively. RESULTS: The mean operation time was significantly increased in the experimental group. The physiological functions and social functions in the two groups were remarkably augmented after 6 months of surgery. However, there was no significant difference in the scores of speech and taste between the two groups at the indicated time of 1 month and 6 months. In addition, the scores for appearance, satisfaction with appearance, role-physical, bodily pain, and general health in the experimental group were better than those in the control group at 1 month and 6 months after surgery. CONCLUSION: The single-port access transaxillary totally endoscopic thyroidectomy is safe and feasible for the treatment of patients with PTC. The subjects who underwent this technique have a good perception of their general state of health and are likely to participate in social activities. It is worthy of being clinically used for patients with PTC.
RESUMO
BACKGROUND: Increasing evidence indicated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acted as a key regulator in the proliferation and invasion of several cancers. However, the function of MALAT1 in the development of thyroid cancer has not been experimentally established. METHODS: The expression of MALAT1 and IQGAP1 in thyroid cancer tissues and cells were detected by quantitative real-time PCR and western blot. The effects of MALAT1 and IQGAP1 on the cell proliferation and invasion of thyroid cancer cells were detected with a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium 4 (MTT) assay and a Transwell assay, respectively. FTC-133 or SW1736 transfected with si-MALAT1 or pcDNA-MALAT1 were injected subcutaneously into 4-week-olds BALB/c mice to examine the impact of MALAT1 on the tumor development of thyroid cancer in vivo. RESULTS: In this study, we discovered the higher level of MALAT-1 and expression of IQGAP1 in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. MTT and Transwell assay showed that the proliferation and invasion of FTC-133 cells with MALAT-1 knockdown were inhibited. Moreover, MALAT-1 could upregulate the expression of IQGAP1 in thyroid cancer cells. In addition, IQGAP1 knockdown reversed the decreasing cell proliferation and invasion of thyroid cancer induced by MALAT-1 overexpression. Finally, the study in vivo verified that MALAT-1 promoted the tumor growth of thyroid cancer. CONCLUSION: Our study indicated that MALAT1 promoted the proliferation and invasion of thyroid cancer cells via regulating the expression of IQGAP1.
Assuntos
Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Proteínas Ativadoras de ras GTPase/genética , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Invasividade Neoplásica , RNA Longo não Codificante/genética , Tela Subcutânea/patologia , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Ativadoras de ras GTPase/metabolismoRESUMO
The acute toxicities of five naphthoquinone compounds to Photobacterium phosphoreum were determined. We evaluated the mechanism of toxicity using the structure-activity relationship technique. The results showed that some factors, including the species of substituents, shape/size of molecule and oil-water partition coefficient (log P) played the important roles in the interaction between the naphthoquinones and the target. Among of these, the toxicities of Atovaquone and Buparvaquone were lower than the other naphthoquinones we tested because of the alkyl-substitution with the bigger volume and strong hydrophobicity. Conversely, Menadione had the highest toxicity because of the appropriate log P and shape/size of molecule resulting in the easier interaction with the target.