| BACKGROUNDColon cancer is one of the most common cancers worldwide,which has high morbidity and mortality globally ranking both the third.Colon cancer prevention and threapy are not good in our country,the morbidity and mortality have an obvious rise in nearly 30 years,and there are more than 170000 new cases annually.Among all the cancers,the mortality of colon cancer ranked the fifth after the lung cancer,liver cancer,gastric cancer and esophageal cancer;the morbidity of it ranked the third after the lung cancer and stomach cancer.With the rapid development of medicine,the therapy for colon cancer has made obvious progress,but the therapy for advanced malignant colon cancer isn't ideal at present,most patients cannot be cured,and eventually died of recurrence and metastasis.Jade family PHD finger 3(JADE3)plays a role in inducing histone acetylation during transcription,and is involved in the progression of several human cancers;however,its role in colon cancer remains unclear.Herein,we found that JADE3 was markedly upregulated in colon cancer tissues and significantly correlated with cancer progression,and predicted shorter patient survival.Further,JADE3 was expressed much higher in colon cancer cell lines that are enriched with a stem-like signature.Overexpression of JADE3 increased,while silencing JADE3 reduced cancer stem cell-like traits in colon cancer cells in vitro and in vivo.Importantly,silencing of JADE3 strongly impaired the tumor initiating capacity of colon cancer cells in vivo.Furthermore,JADE3 interacted with the promoters of colon stem cell marker LGR5 and activated its transcription,by increasing the occupancy of p300 acetyltransferase and histone acetylation on the promoters.Finally,we found that JADE3 expression was substantially induced by Wnt/p-catenin signaling.These findings suggest an oncogenic role of JADE3 by regulating cancer stem cell-like traits in the colon cancer,and therefore JADE3 might be a potential therapeutic target for the treatment of colon cancer.Methods1,Various public database,including TCGA database and GSE,Real-time PCR and Western blot analysis were used to analyse the expression of JADE3 in colon cancer.2.Immunohistochemistry and clinical information were used to analyse the relationship between clinical parameters and the expression of JADE3.3.Gene Set Enrichment analysis,Sphere formation and Flow cytometry were used to identify the change of colon cancer cells sternness when interfered with JADE3.4.Tumor xenografts were used to analysis the influence of JADE3 silencing on the capacity of tumorigenesis.5.Real-time PCR and Western blot were used to analysis the influence of JADE3 on the expression of LGR5;Chip analysis was used to identify whether JADE3 could enhance LGR5 transcription by increasing the enrichment of p300 and histone acetylation in its promoter;this section aims to explore the specific molecular mechanism of how does JADE3 regulate the sternness of colon cancer?6,Real-time PCR and Western blot were used to analysis the expression of JADE3 when colon cancer cells were treated differently;this section aims to explore the specific upstream regulatory mechanism of the upregulation of JADE3 in colon cancer.Results:1.JADE3 is markedly upregulated in colon cancer2.Upregulation of JADE3 is associated with poor prognosis in colon cancer3.JADE3 increases the self-renewal capacity of colon cancer cells in vitro4.Silencing of JADE3 inhibits colon cancer initiation in vivo5.JADE3 enhances LGR5 transcription by increasing the enrichment of p300 and histone acetylation in its promoter6.JADE3 is induced by Wnt/?-catenin signaling... |
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