ABSTRACT
OBJECTIVE: Accumulating evidence indicates that circular RNAs (circRNAs) contribute to breast cancer (BC) development and progression. However, the role of circ_0058063 in BC and its underlying molecular processes remain unclear. METHODS: The expression of circ_0058063, miR-557, and DLGAP5 in BC tissues and cells was determined using real time quantitative PCR or western blotting. The functions of circ_0058063 in BC cells were detected using CCK-8, Transwell, caspase-3 activity, and xenograft tumor assays. The specific binding of circ_0058063/miR-557 and DLGAP5/miR-557 was verified using RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. RESULTS: circ_0058063 expression was upregulated in BC tissues and cells. circ_0058063 knockdown inhibited proliferation and migration but promoted apoptosis in MCF-7 and MDA-MB-231 cells in vitro. In vivo studies further validated that the knockdown of circ_0058063 repressed tumor growth. Mechanistically, circ_0058063 directly sponged miR-557 and negatively regulated its expression. Additionally, miR-557 inhibition reversed the tumor-suppressive effects of the circ_0058063 knockdown on the survival of MDA-MB-231 and MCF-7 cells. Moreover, miR-557 directly targeted DLGAP5. DLGAP5 knockdown suppressed MCF-7 and MDA-MB-231 cell growth, and these effects were reversed by miR-557 downregulation. CONCLUSION: Our findings verify that circ_0058063 acts as a sponge for miR-557 to upregulate DLGAP5 expression. These findings suggest that the circ_0058063/miR-557/DLGAP5 axis is an important regulator of oncogenic function and may be a promising therapeutic target for BC.
Subject(s)
Breast Neoplasms , MicroRNAs , Female , Humans , Apoptosis/genetics , Blotting, Western , Breast , Breast Neoplasms/genetics , Cell Proliferation/genetics , MicroRNAs/genetics , Neoplasm Proteins , RNA, Circular/geneticsABSTRACT
BACKGROUND: Breast cancer has recently become one of the most common causes of cancer-related deaths, and several studies have suggested that genetic polymorphisms in the folate metabolism pathway may be associated with susceptibility to breast cancer, although their results have been inconsistent or inconclusive. Therefore, the aim of this meta-analysis was to obtain accurate, consistent conclusions regarding the potential associations of genetic polymorphisms in the folate metabolism pathway with the risk of breast cancer, based on case-controlled studies. METHODS: From the beginning of database establishment through May 2021, we indexed and searched domestic and foreign databases, including the Chinese National Knowledge Infrastructure, Web of Science, VIP and BioMedical Database of China, PubMed, EMBASE, Wanfang database, and the Cochrane Library. To determine the effects of folate metabolism-related genetic polymorphisms on breast cancer risk, we used Stata version 16.0 to analyze all data and calculated variable odds ratios and 95% confidence intervals. RESULTS: The findings of the current meta-analysis are going to be presented to peer-reviewed journals for publication when the analysis is completed. CONCLUSION: The meta-analysis will summarize the association of genetic polymorphisms in the folate metabolism pathway with breast cancer. REGISTRATION NUMBER: May 26, 2021.osf.io/25r48. (https://osf.io/25r48/).
Subject(s)
Breast Neoplasms/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Breast Neoplasms/metabolism , Female , Humans , Meta-Analysis as TopicABSTRACT
BACKGROUND: Considering the combined role of long non-coding RNA (lncRNAs)-microRNA (miRNA)-mRNA in tumorigenesis, the purpose of this study was to investigate how TNRC6C-AS1 regulates the expression of lysophosphatidic acid receptor 5 (LPAR5) by modulating miR-513c-5p, thus influencing the progression of thyroid cancer (THCA). METHODS: qRT-PCR and Western blotting were performed to detect the expression levels of TNRC6C-AS1, miR-513c-5p, and LPAR5 in THCA tissues and cell lines. The viability, proliferation, migration, and invasion were assessed using CCK-8, BrdU, wound healing, and transwell migration assays, respectively. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were used to evaluate the relationship between TNRC6C-AS1, miR-513c-5p, and LPAR5. RESULTS: TNRC6C-AS1 was highly expressed in THCA tissues, and knockout of TNRC6C-AS1 reduced the viability, proliferation, migration, and invasion of THCA cells. TNRC6C-AS1 competitively adsorbed miR-513c-5p. In addition, the biological function of TNRC6C-AS1 was blocked by knocking down the thyroid cell line TNRC6C-AS1 with miR-513c-5p inhibitor transfection. LPAR5 is the target gene for miR-513c-5p, which has the ability to eliminate the influence of miR-513c-5p on THCA cells. CONCLUSION: The TNRC6C-AS1/miR-513c-5p/LPAR5 axis is a novel signaling pathway that modulates THCA progression and may be a potential target for cancer therapy.
ABSTRACT
BACKGROUND: Despite the developments in diagnosis and treatment of HER2-positive metastatic breast cancer, there is a high likelihood in the development of resistance to trastuzumab. In general, HER2-positive patients with deteriorated health face negative clinical outcomes. The present study is conducted to systematically explore the medicinal properties of trastuzumab in HER2-positive breast cancer patients. METHODS: Randomized controlled trials investigating the clinical properties of including trastuzumab to treat HER2-positive breast cancer cases will be sourced by exploring these online-based databases: MEDLINE, BIOSIS, China National Knowledge Infrastructure (CNKI), Cochrane Library, EMBASE, Central Register of Controlled Trials, and WanFang. Two independent authors will screen the literature, gather data, and assess the quality of selected studies. The significance of the relationship between the medical properties of trastuzumab when incorporated to treat HER2-positive breast cancer cases will be evaluated according to the relative risk, mean differences or standardized mean differences, and 95% confidence interval. RESULTS: The outcomes from this review shall be issued in a journal that will be reviewed by peers. CONCLUSION: The conclusions presented in this review will serve as a reference for clinical practitioners and scholars to determine whether trastuzumab is an effective and safety intervention for treating HER2-positive breast cancer patients. ETHICS AND DISSEMINATION: Since this study is a systematic review of published studies, an ethical approval is not needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: March 31, 2021.osf.io/wvqkf (https://osf.io/wvqkf/).
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Trastuzumab/therapeutic use , Breast Neoplasms/mortality , Disease-Free Survival , Double-Blind Method , Female , Humans , Meta-Analysis as Topic , Randomized Controlled Trials as Topic , Receptor, ErbB-2/drug effects , Research Design , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.
Subject(s)
Blood Transfusion , Complement Inactivating Agents/therapeutic use , Elapid Venoms/therapeutic use , Graft Rejection/prevention & control , Graft Survival/drug effects , Liver Transplantation/physiology , Transplantation, Heterologous , Animals , Drug Evaluation, Preclinical , Female , Graft Rejection/immunology , Graft Survival/immunology , Guinea Pigs , Liver Transplantation/immunology , Liver Transplantation/mortality , Male , Perfusion , Random Allocation , Rats , Rats, Sprague-Dawley , Transplantation, Heterologous/immunology , Transplantation, Heterologous/mortality , Transplantation, Heterologous/pathologyABSTRACT
PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.
OBJETIVO: Investigar a supressão sinérgica da pré-perfusão do doador de fígado com soro do receptor (SR) e tratamento com fator veneno de cobra (FVC) na rejeição hiperaguda (RHA) após o xenotransplante de fígado. MÉTODOS: Foram utilizados Cobaias (GP, n=24) e ratos Sprague-Dawley (SD, n=24). Antes do transplante foram coletadas amostras de soro dos ratos SD e usados para a preparação dos complementos inativados. Cobaias GP e ratos SD foram randomicamente distribuídos em quatro grupos (n=6), respectivamente: grupo RS, grupo FVC, grupo SR+FVC e grupo controle. Xenotransplante ortotópico do fígado foi realizado com a técnica de dois cuffs modificados. Foram investigados o de tempo de sobrevida, a função hepática dos receptores e alterações morfopatológicas em fígados de ratos. RESULTADOS: Não houve alteração na coloração do parênquima dos fígados nos receptores. O tempo de sobrevida dos receptores em todos os grupos experimentais foi mais longo do que o grupo controle (p<0,05). Além disso, o tempo de sobrevida do grupo SR+ FVC foi marcadamente maior do que o grupo SR (p<0,01) e o grupo FVC (p<0,05). O nível sérico ALT foi menor em todos os grupos experimentais do que o grupo controle (p<0,05). O nível de ALT no grupo SR+ FVC foi significantemente menor do que no grupo FVC (p<0,05) e o grupo SR (p<0,01). As alterações histológicas foram significantemente melhoradas quando comparado com o grupo controle, e os danos histológicos no grupo SR+ FVC foram mais moderados do que nos grupos restantes (p<0,05). CONCLUSÃO: Pré-perfusão do fígado doador com soro do receptor e fator veneno de cobra pode exercer efeito supressor sinérgico da rejeição hiperaguda após xenotransplante de fígado.
