Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we ident...Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.展开更多
The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determin...The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determined the function of E2F4 in the silkworm,Bombyx mori.We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals.Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase,whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase.These results indicate that BmE2F4 is important in cell cycle regulation.We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk gland.Furthermore,we identified a protein called Bm14-3-3ζthat can interact with BmE2F4 and allow it to localize in the nucleus.Overexpression of the Bm14-3-3ζgene led to cell cycle arrest in the G1 phase,while knocking down the gene increased the proportion of cells in S phase.These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation.展开更多
基金This study was supported by Shanghai Changning District Committee of Science and Technology(CNKW2016Y01)Shanghai Tongren Hospital Project(TRYJ201501)+3 种基金Suzhou Science and Technology Development Program(SYS201717)the Second Affiliated Hospital of Soochow University Advance Research Program of the Natural Science Foundation of China Grants(SDFEYGJ1705)Open project of Jiangsu State Key Laboratory of Radiation Medicine and Projection(GJS1963)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Transforming growth factor-β1(TGF-β1)acts as a tumor promoter in advanced prostate cancer(PCa).We speculated that microRNAs(miRNAs)that are inhibited by TGF-β1 might exert anti-tumor effects.To assess this,we identified several miRNAs downregulated by TGF-β1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA.miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue,and its expression level correlated inversely with aggressive clinical pathological features.Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation,migration,and invasion,and promoted apoptosis.The miR-3691-3p target genes E2F transcription factor 3(E2F3)and PR domain containing 1,with ZNF domain(PRDM1)were upregulated in miR-3691-3p-overexpressing PCa cells,and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation,migration,and invasion.Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis.Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p,both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue.Our results indicate that TGF-β1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1.These results provide novel insights into the mechanisms by which TGF-β1 contributes to the progression of PCa.
基金We thank Dr.Jiangbo Song for phylogenetic analysis.This research was funded by National Natural Science Foundation of China(31872428 and 31872427)Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0096 and estc 2020jscx-msxmX0045)China Agriculture Research System(CARS-18).
文摘The E2F family of transcription factors is crucial for cell cycle progression and cell fate decisions.Although E2Fs have been widely studied in mammals,there have been few studies performed in insects.Here,we determined the function of E2F4 in the silkworm,Bombyx mori.We demonstrate that E2F proteins are highly conserved among species from lower animals to higher mammals.Overexpression of the BmE2F4 gene led to cell cycle arrest in the G1 phase,whereas interfering with the BmE2F4 mRNA led to accumulation of cells in the S phase.These results indicate that BmE2F4 is important in cell cycle regulation.We also demonstrate that the BmE2F4 gene is involved in DNA replication of BmN-SWU1 cells and DNA synthesis in the silk gland.Furthermore,we identified a protein called Bm14-3-3ζthat can interact with BmE2F4 and allow it to localize in the nucleus.Overexpression of the Bm14-3-3ζgene led to cell cycle arrest in the G1 phase,while knocking down the gene increased the proportion of cells in S phase.These findings provide important insights into the function of E2F transcription factors and increase our understanding of their involvement in cell cycle regulation.
