ABSTRACT
OBJECTIVE: In recent years, the incidence of papillary thyroid carcinoma (PTC) has increased. Many microRNAs (miRNAs) have been found to regulate PTC progression. However, the regulatory mechanism of miR-219 remains unclear in PTC. Therefore, the purpose of this study is to explore the function of miR-219 in PTC. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot analysis were used to detect the expression of miR-219 and eyes absent homologue 2 (EYA2). The function of miR-219 was investigated by methyl thiazolyl tetrazolium (MTT) and transwell assays. The relationship between miR-219 and EYA2 was confirmed by Dual-Luciferase reporter assay. RESULTS: MiR-219 expression was reduced and was associated with TNM stage and lymph node metastases in PTC patients. Functionally, overexpression of miR-219 restrained the viability and metastasis of PTC cells. In addition, miR-219 induced apoptosis and blocked EMT in PTC cells. Furthermore, miR-219 was confirmed to directly target EYA2 and inhibited its expression in PTC. More importantly, the upregulation of EYA2 impaired the inhibitory effect of miR-219 in PTC. CONCLUSIONS: MiR-219 inhibits the viability and metastasis of PTC cells by downregulating EYA2.
Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , MicroRNAs/metabolism , Nuclear Proteins/metabolism , Protein Tyrosine Phosphatases/metabolism , Thyroid Cancer, Papillary/metabolism , Thyroid Neoplasms/metabolism , Apoptosis , Cell Proliferation , Cell Survival , Cells, Cultured , Female , Humans , Male , MicroRNAs/genetics , Middle Aged , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathologyABSTRACT
Objective: To explore HIV-1 drug resistance and influencing factors among people living with HIV/AIDS before antiretroviral therapy in Liangshan Yi Autonomous Prefecture (Liangshan). Methods: Between January 1 and June 30, in both 2017 and 2018, a cross-sectional survey was conducted in Liangshan HIV-1 pol sequences were gathered and analyzed according to WHO Guidelines on HIV drug resistance surveillance of 2014. Both HyPhy 2.2.4 and Cytoscape 3.6.1 software were used to analyze the drug resistant strains of HIV-1 transmission network. Results: A total of 464 people living with HIV/AIDS was recruited. The proportion of HIV-1 CRF07_BC subtype was 88.6% (411/464), with HIV-1 drug resistance rate was 9.9% (46/464). The HIV-1 drug resistance rates of non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors(NRTI) and protease inhibitors (PI) were 6.7% (31/464), 1.9% (9/464) and 0.4% (2/464) respectively. New recombinant strains of HIV-1 URF_01BC subtype was independently clustered according to the drug resistant mutation sites. Results from the multivariate logistic analysis showed that injected drug users group had higher risk on HIV-1 drug resistance (aOR=3.03, 95%CI:1.40-6.54) than heterosexual group among people living with HIV/AIDS. Conclusions: HIV-1 drug resistance rate had already been in a high level before antiretroviral therapy was in place. The newly identified recombinant strains of HIV-1 URF_01BC subtype were independently clustered according to the drug resistant mutation sites. It was necessary to strengthen the prevention of the HIV-1 drug resistant strains transmission.
Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , China/epidemiology , Cross-Sectional Studies , HIV Infections/epidemiology , HIV-1/isolation & purification , Humans , Mutation , Sequence Analysis, DNA , Viral LoadABSTRACT
BACKGROUND: A number of putative roles, including the modulation of tumor growth, neovascularization, metastasis and oncogenic progression, have been correlated to relaxin-2 overexpression. However, the clinical significance of relaxin-2 expression in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the expression of relaxin-2 in HCC and determine its correlation with tumor progression and prognosis. PATIENTS AND METHODS: 180 HCC patients who had undergone curative liver resection were selected and immunohistochemistry was performed to analyze relaxin-2 expression in the respective tumors. RESULTS: Immunohistochemistry confirmed relaxin-2 overexpression in HCC tissues compared with their adjacent nonneoplastic tissues (p < 0.01). Additionally, immunostaining showed more relaxin-2 positive cells in the higher tumor grade (III) than in the lower tumor stage (I, II; p = 0.026). Moreover, HCC patients with high relaxin-2 expression were significantly associated with lower 5-year overall survival (p < 0.01) and lower 5-year disease-free survival (p < 0.01), respectively. Furthermore, immunostaining showed more relaxin-2 positive cells in the tumor recurrence (ETR) patients than non-ETR patients (p = 0.001). The Cox proportional hazards model further showed that relaxin-2 was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 1.872, 95% confidence interval [CI] = 1.18-5.146, p = 0.023) and 5-year overall survival (HR = 3.637, CI = 1.443-7.15, p = 0.001) in HCC. CONCLUSIONS: Our data suggest for the first time that the overexpression of relaxin-2 protein in HCC tissues is of predictive value on tumor progression and poor prognosis.
