BACKGROUND Recent studies have emphasized the emerging importance of long noncoding RNAs(lncRNAs)in colorectal cancer(CRC).However,the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully...BACKGROUND Recent studies have emphasized the emerging importance of long noncoding RNAs(lncRNAs)in colorectal cancer(CRC).However,the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated.AIM To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC.METHODS TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC,and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed.The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in vivo.Mechanistically,we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA.RESULTS TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients.A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation,migration ability and invasion ability of colon cancer cells in vitro and in vivo.A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression,ultimately promoting colorectal tumorigenesis and progression.CONCLUSION TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC,indicating that it may be a novel target for CRC therapy.展开更多
Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievi...Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievirus B5(CVB5)infection remain unknown.Here,we identified a novel cytoplasmic lncRNA,LINC1392,which was highly inducible in CVB5 infected RD cells in a time-and dose-dependent manner,and also can be induced by the viral RNA and IFN-β.Further investigation showed that LINC1392 promoted several important interferon-stimulated genes(ISGs)expression,including IFIT1,IFIT2,and IFITM3 by activating MDA5,thereby inhibiting the replication of CVB5 in vitro.Mechanistically,LINC1392 bound to ELAV like RNA binding protein 1(ELAVL1)and blocked ELAVL1 interaction with MDA5.Functional study revealed that the 245–835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding.In mice,LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection.Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection.Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.展开更多
基金The study was reviewed and approved by the Ethics Committee of the Second Hospital of Hebei Medical University(No.2021-R241).
文摘BACKGROUND Recent studies have emphasized the emerging importance of long noncoding RNAs(lncRNAs)in colorectal cancer(CRC).However,the functions and regulatory mechanisms of numerous lncRNAs in CRC have not been fully elucidated.AIM To explore the functional role and underlying molecular mechanisms of lncRNA TNFRSF10A-AS1 in CRC.METHODS TNFRSF10A-AS1 expression was measured by quantitative real-time polymerase chain reaction in CRC,and the relationship between TNFRSF10A-AS1 levels and the clinicopathological features of CRC patients was analyzed.The effect of TNFRSF10A-AS1 expression on CRC proliferation and metastasis was examined in vitro and in vivo.Mechanistically,we investigated how TNFRSF10A-AS1 is involved in CRC as a competitive endogenous RNA.RESULTS TNFRSF10A-AS1 was expressed at a high level in CRC and the upregulation of TNFRSF10A-AS1 was associated with advanced T grade and tumor size in CRC patients.A functional investigation revealed that TNFRSF10A-AS1 enhanced the proliferation,migration ability and invasion ability of colon cancer cells in vitro and in vivo.A mechanistic analysis demonstrated that TNFRSF10A-AS1 acted as a miR-3121-3p molecular sponge to regulate HuR expression,ultimately promoting colorectal tumorigenesis and progression.CONCLUSION TNFRSF10A-AS1 exerts a tumor-promoting function through the miR-3121-3p/HuR axis in CRC,indicating that it may be a novel target for CRC therapy.
基金This work was supported by the National Natural Science Foundation of China(No.81860357)the Young Talents Support Program of Yunnan Province,China(Ten Thousand People Plan,YNWR-QNBJ-2019-178).
文摘Long noncoding RNAs(lncRNAs)modulate many aspects of biological and pathological processes.Recent studies have shown that host lncRNAs participate in the antiviral immune response,but functional lncRNAs in coxsackievirus B5(CVB5)infection remain unknown.Here,we identified a novel cytoplasmic lncRNA,LINC1392,which was highly inducible in CVB5 infected RD cells in a time-and dose-dependent manner,and also can be induced by the viral RNA and IFN-β.Further investigation showed that LINC1392 promoted several important interferon-stimulated genes(ISGs)expression,including IFIT1,IFIT2,and IFITM3 by activating MDA5,thereby inhibiting the replication of CVB5 in vitro.Mechanistically,LINC1392 bound to ELAV like RNA binding protein 1(ELAVL1)and blocked ELAVL1 interaction with MDA5.Functional study revealed that the 245–835 nt locus of LINC1392 exerted the antiviral effect and was also an important site for ELAVL1 binding.In mice,LINC1392 could inhibit CVB5 replication and alleviated the histopathological lesions of intestinal and brain tissues induced by viral infection.Our findings collectively reveal that the novel LINC1392 acts as a positive regulator in the IFN-I signaling pathway against CVB5 infection.Elucidating the underlying mechanisms on how lncRNA regulats the host innate immunity response towards CVB5 infection will lay the foundation for antiviral drug research.
