Many circular RNAs(circRNAs)are reported to be abnormally expressed during the progression of various tumors,and these circRNAs can be used as anti-tumor targets.Therefore,it is important to identify circRNAs that can...Many circular RNAs(circRNAs)are reported to be abnormally expressed during the progression of various tumors,and these circRNAs can be used as anti-tumor targets.Therefore,it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer(CRC).Here,we report that hsa_Circ_0000826(Circ_0000826),a circ RNA with significantly reduced expression level in CRC tissues,is associated with a poor prognosis in patients.The silencing of Circ_0000826 promotes the proliferation of CRC cells.Conversely,the overexpression of Circ_0000826 restricted CRC cell proliferation both in vitro and in vivo.Furthermore,Circ_0000826 could target AU-rich element RNA-binding protein 1(AUF1).AUF1,known as heterogeneous nuclear ribonucleoprotein D(hnRNP D),could bind to the c-MYC 3’-UTR and promote c-MYC expression.When Circ_0000826 binds to AUF1,it competitively inhibits the binding of AUF1 to the c-MYC 3’-UTR,which inhibits the c-MYC expression and cell proliferation.These results provide novel insights into the functional mechanism of Circ_0000826 action in CRC progression and indicate its potential use as a therapeutic target in CRC.展开更多
Background Coronary microembolization （CME） is characterized by distal microvascular occlusion. However, the inflammatory mechanisms and therapeutic targets of CME are largely unknown. Methods A total of 11 Guangxi ...Background Coronary microembolization （CME） is characterized by distal microvascular occlusion. However, the inflammatory mechanisms and therapeutic targets of CME are largely unknown. Methods A total of 11 Guangxi Bama miniature swines were divided into two groups： sham （n = 5） and CME （n = 6）. Microspheres were injected into the left anterior descending artery of the CME group to make an animal model of CME. The expres- sions of microRNA-146a （miR-146a） and IRAK1, TRAF6, and AUF1 in the myocardium were detected by qPCR. Results In the CME group, microspheres, microinfarction, and inflammatory cell infiltration were found under an optical microscope. The expression levels of miR-146a were low in both groups. After CME, the expression levels of IRAK1, TRAF6, and AUF1 in the CME group were upregulated compared with those in the sham group （P 〈 0.01;P 〈 0.05;P 〈 0.05, respectively）. Conclusions AUF1, IRAK1 and TRAF6, but not miR-146a, could be involved, in myocardium inflammation following CME.展开更多
Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal conse-quences.Despite identifying i...Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal conse-quences.Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is evident.In our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus barrier.This enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory response.Importantly,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs.Mechanistically,E.copr up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells.An espe-cially significant finding is that E.copr activates the AhR pathway,thereby promoting the expression of AUF1.In summary,our results strongly indicate that E.copr enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.81802470,31800658,and U1804173)the Department of Science and Technology,Henan Province(Grant Nos.212102310621 and 192102310362)+1 种基金Joint construction project of Henan Medical Science and technology research plan(No.LHGJ20210910)the Xinxiang Medical University research funding(Grant No.XYBSKYZZ201632)。
文摘Many circular RNAs(circRNAs)are reported to be abnormally expressed during the progression of various tumors,and these circRNAs can be used as anti-tumor targets.Therefore,it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer(CRC).Here,we report that hsa_Circ_0000826(Circ_0000826),a circ RNA with significantly reduced expression level in CRC tissues,is associated with a poor prognosis in patients.The silencing of Circ_0000826 promotes the proliferation of CRC cells.Conversely,the overexpression of Circ_0000826 restricted CRC cell proliferation both in vitro and in vivo.Furthermore,Circ_0000826 could target AU-rich element RNA-binding protein 1(AUF1).AUF1,known as heterogeneous nuclear ribonucleoprotein D(hnRNP D),could bind to the c-MYC 3’-UTR and promote c-MYC expression.When Circ_0000826 binds to AUF1,it competitively inhibits the binding of AUF1 to the c-MYC 3’-UTR,which inhibits the c-MYC expression and cell proliferation.These results provide novel insights into the functional mechanism of Circ_0000826 action in CRC progression and indicate its potential use as a therapeutic target in CRC.
基金supported by Guangxi Province Medical Technology Research and Development Project(Grant No.S201303_01)Youth Science Foundation of Guangxi Medical University(No.GXMUYSF201213)
文摘Background Coronary microembolization （CME） is characterized by distal microvascular occlusion. However, the inflammatory mechanisms and therapeutic targets of CME are largely unknown. Methods A total of 11 Guangxi Bama miniature swines were divided into two groups： sham （n = 5） and CME （n = 6）. Microspheres were injected into the left anterior descending artery of the CME group to make an animal model of CME. The expres- sions of microRNA-146a （miR-146a） and IRAK1, TRAF6, and AUF1 in the myocardium were detected by qPCR. Results In the CME group, microspheres, microinfarction, and inflammatory cell infiltration were found under an optical microscope. The expression levels of miR-146a were low in both groups. After CME, the expression levels of IRAK1, TRAF6, and AUF1 in the CME group were upregulated compared with those in the sham group （P 〈 0.01;P 〈 0.05;P 〈 0.05, respectively）. Conclusions AUF1, IRAK1 and TRAF6, but not miR-146a, could be involved, in myocardium inflammation following CME.
基金This work was supported by the National Natural Science Foundation of China(No.82373910,82204409)The“Double First-Class”University Project(CPU2022QZ20,China)。
文摘Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal conse-quences.Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is evident.In our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus barrier.This enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory response.Importantly,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs.Mechanistically,E.copr up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells.An espe-cially significant finding is that E.copr activates the AhR pathway,thereby promoting the expression of AUF1.In summary,our results strongly indicate that E.copr enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.
