Renal cell carcinoma(RCC)has a poor prognosis due to limited diagnosis and treatment.Thus,it is necessary to find novel prognostic biomarkers and therapeutic targets.The aberrant expression of microRNAs plays an impor...Renal cell carcinoma(RCC)has a poor prognosis due to limited diagnosis and treatment.Thus,it is necessary to find novel prognostic biomarkers and therapeutic targets.The aberrant expression of microRNAs plays an important role in RCC oncogenesis.Tissue inhibitors of metalloproteinase 3(TIMP3)acts as a downstream target of miR-181b.The aim of this study was to understand the role and molecular mechanism of miR-181b in RCC oncogenesis.The results showed that miR-181b expression was significantly higher in RCC tumour tissues,especially in those with significant invasion or metastasis.miR-181b overexpression promoted proliferation and migration of the RCC cell line 786-O,while miR-181b knockdown had the opposite effect.In addition,miR-181b was inversely correlated with TIMP3 expression in RCC tumour tissues.miR-181b overexpression reduced TIMP3 expression in RCC cell line 786-O or OS-RC-2,while miR-181b knockdown had the inverse effect.Mechanistically,a luciferase reporter assay confirmed the binding sites of miR-181b on the 3’-UTR of TIMP3,confirming the targeting effect of miR-181b on TIMP3.Overall,miR-181b promotes the development and progression of RCC by targeting TIMP3 expression,indicating the potential use of miR-181b in the diagnosis and treatment of RCC.展开更多
Programmed cell death 4 （PDCD4） is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer （CRC）. During CRC carcinogenesis, PDCD4 protein levels remarkably decrease...Programmed cell death 4 （PDCD4） is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer （CRC）. During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and conse- quently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken toge- ther, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.展开更多
基金This work was supported by grants Basic Scientific Research Projects of Fujian Provincial Public Welfare Scientific Research Institutes(2016R1029-2).
文摘Renal cell carcinoma(RCC)has a poor prognosis due to limited diagnosis and treatment.Thus,it is necessary to find novel prognostic biomarkers and therapeutic targets.The aberrant expression of microRNAs plays an important role in RCC oncogenesis.Tissue inhibitors of metalloproteinase 3(TIMP3)acts as a downstream target of miR-181b.The aim of this study was to understand the role and molecular mechanism of miR-181b in RCC oncogenesis.The results showed that miR-181b expression was significantly higher in RCC tumour tissues,especially in those with significant invasion or metastasis.miR-181b overexpression promoted proliferation and migration of the RCC cell line 786-O,while miR-181b knockdown had the opposite effect.In addition,miR-181b was inversely correlated with TIMP3 expression in RCC tumour tissues.miR-181b overexpression reduced TIMP3 expression in RCC cell line 786-O or OS-RC-2,while miR-181b knockdown had the inverse effect.Mechanistically,a luciferase reporter assay confirmed the binding sites of miR-181b on the 3’-UTR of TIMP3,confirming the targeting effect of miR-181b on TIMP3.Overall,miR-181b promotes the development and progression of RCC by targeting TIMP3 expression,indicating the potential use of miR-181b in the diagnosis and treatment of RCC.
文摘Programmed cell death 4 （PDCD4） is a RNA-binding protein that acts as a tumor suppressor in many cancer types, including colorectal cancer （CRC）. During CRC carcinogenesis, PDCD4 protein levels remarkably decrease, but the underlying molecular mechanism for decreased PDCD4 expression is not fully understood. In this study, we performed bioinformatics analysis to identify miRNAs that potentially target PDCD4. We demonstrated miR-181b as a direct regulator of PDCD4. We further showed that activation of IL6/STAT3 signaling pathway increased miR-181b expression and conse- quently resulted in downregulation of PDCD4 in CRC cells. In addition, we investigated the biological effects of PDCD4 inhibition by miR-181b both in vitro and in vivo and found that miR-181b could promote cell proliferation and migration and suppress apoptosis in CRC cells and accelerate tumor growth in xenograft mice, potentially through targeting PDCD4. Taken toge- ther, this study highlights an oncomiR role for miR-181b in regulating PDCD4 in CRC and suggests that miR-181b may be a novel molecular therapeutic target for CRC.
