ABSTRACT
MicroRNAs have been reported to play a crucial role in ovarian cancer (OC) as the most lethal malignancy of the women.Here, we found miR-506-3p was significantly down-regulated in OC tissues compared with corresponding adjacent nontumor tissues. Ectopic miR-506-3p expression inhibited OC cell growth and proliferation using MTT and colony formationassay. Additionally, flow cytometry analysis showed that the overexpression of miR-506-3p induced cell cycle G0/G1phase arrest and cell apoptosis in OC cells. A luciferase reporter assay confirmed that the myotubularin-related protein 6(MTMR6) was the target of miR-506-3p. The expression of MTMR6 was increased in OC tissues compared with adjacenttissues using immunohistochemistry. Elevated MTMR6 protein levels were confirmed in OC cells lines compared withimmortalized fallopian tube epithelial cell line FTE187 using western blotting. In addition, knockdown of MTMR6 imitatedthe effects of miR-506-3p on cell proliferation, cell cycle progression and apoptosis in OC cells. Furthermore, rescueexperiments using MTMR6 overexpression further verified that MTMR6 was a functional target of miR-506-3p. Our dataindicate that miR-506-3p might serve as a tumor suppressor gene and propose a new regulatory mechanism of MTMR6 bymiR-506-3p in OC.
ABSTRACT
Objectives: Men who have sex with men are at risk of tenofovir nephrotoxicity due to its wide use in both treatment and prophylaxis for human immunodeficiency virus infection, but little is known about the urinary biomarkers of early renal dysfunction in this population. This study aims to identify useful biomarkers of early renal dysfunction among human immunodeficiency virus-infected men who have sex with men exposed to tenofovir.Methods: In a cross-sectional study urinary alpha1-microglobulin, beta2-microglobulin, N-acetyl-B-n-glucosaminidase and albumin were measured and expressed as the ratio-to-creatinine in 239 human immunodeficiency virus-infected men who have sex with men who were treatment naïve or receiving antiretroviral therapy with tenofovir-containing or non-tenofovir-containing regimens. Additionally, 56 patients in the non-antiretroviral therapy group started a tenofovir-containing regimen and were assessed after 3 and 6 months on antiretroviral therapy.Results: Both the frequency of alpha1-microglobulin proteinuria (alpha1-microglobulin-creatinine ratio >25.8 mg/g) and the median urinary alpha1-microglobulin-creatinine ratio were higher in the tenofovir disoproxil fumarate group than the other two groups (all p< 0.05). A higher frequency of beta2-microglobulin proteinuria (beta2-microglobulin-creatinine ratio >0.68 mg/g) was also observed in the tenofovir group (28.9%) compared to the non-tenofovir group (13.6%, p= 0.024). There were no significant differences between groups for N-acetyl-β-n-glucosaminidase and albumin. In the longitudinal study, the median urinary alphat-microglobulin-creatinine ratio after 3 and 6 months on tenofovir-containing therapy (16.8 and 17.3 mg/g) was higher than baseline (12.3 mg/g, p= 0.023 and 0.011, respectively), while no statistically important changes were observed in urinary beta2-microglobulin-creatinine ratio or in the other biomarkers after 3 and 6 months on antiretroviral therapy (all p> 0.05).Conclusion: Urinary alphat-microglobulin seems to be a more sensitive and stable indicator of tubular dysfunction than urinary beta2-microglobulin for assessing tenofovir-related nephrotoxicity and can be significantly altered after tenofovir exposure.