{"data":{"id":"10.6084/m9.figshare.c.2128316","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2128316","prefix":"10.6084","suffix":"m9.figshare.c.2128316","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Huang, ShuYa","givenName":"ShuYa","familyName":"Huang","affiliation":[],"nameIdentifiers":[]},{"name":"Lu, Wei","givenName":"Wei","familyName":"Lu","affiliation":[],"nameIdentifiers":[]},{"name":"Ge, Di","givenName":"Di","familyName":"Ge","affiliation":[],"nameIdentifiers":[]},{"name":"Meng, Ning","givenName":"Ning","familyName":"Meng","affiliation":[],"nameIdentifiers":[]},{"name":"Li, Ying","givenName":"Ying","familyName":"Li","affiliation":[],"nameIdentifiers":[]},{"name":"Su, Le","givenName":"Le","familyName":"Su","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, ShangLi","givenName":"ShangLi","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Yun","givenName":"Yun","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Zhao, BaoXiang","givenName":"BaoXiang","familyName":"Zhao","affiliation":[],"nameIdentifiers":[]},{"name":"Miao, JunYing","givenName":"JunYing","familyName":"Miao","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"A new microRNA signal pathway regulated by long noncoding RNA TGFB2-OT1 in autophagy and inflammation of vascular endothelial cells"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biochemistry"},{"subject":"Microbiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"Molecular Biology"},{"subject":"Physiology"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Biological Sciences not elsewhere classified"},{"subject":"Developmental Biology"},{"subject":"Science Policy"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"\u003ci\u003eTGFB2-OT1\u003c/i\u003e (\u003ci\u003eTGFB2\u003c/i\u003e overlapping transcript 1) is a newly discovered long noncoding RNA (lncRNA) derived from the 3′UTR of TGFB2. It can regulate autophagy in vascular endothelial cells (VECs). However, the mechanisms of \u003ci\u003eTGFB2-OT1\u003c/i\u003e action are unclear, and whether it is involved in VECs dysfunction needs investigation. Here, the level of \u003ci\u003eTGFB2-OT1\u003c/i\u003e was markedly increased by lipopolysaccharide and oxidized low-density lipoprotein, 2 VECs inflammation triggers. A chemical small molecule, 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one (3BDO) significantly decreased \u003ci\u003eTGFB2-OT1\u003c/i\u003e levels and inhibited the effect of LPS and oxLDL. The NUPR1 level was upregulated by the 2 inflammation inducers and modulated the \u003ci\u003eTGFB2-OT1\u003c/i\u003e level by promoting the expression of TIA1, responsible for \u003ci\u003eTGFB2-OT1\u003c/i\u003e processing. We focused on how \u003ci\u003eTGFB2-OT1\u003c/i\u003e regulated autophagy and inflammation. Use of miRNA chip assay, \u003ci\u003eTGFB2-OT1\u003c/i\u003e overexpression technology and 3BDO revealed that \u003ci\u003eTGFB2-OT1\u003c/i\u003e regulated the levels of 3 microRNAs, \u003ci\u003eMIR3960, MIR4488\u003c/i\u003e and \u003ci\u003eMIR4459\u003c/i\u003e. Further studies confirmed that \u003ci\u003eTGFB2-OT1\u003c/i\u003e acted as a competing endogenous RNA, bound to \u003ci\u003eMIR3960, MIR4488\u003c/i\u003e and \u003ci\u003eMIR4459\u003c/i\u003e, then regulated the expression of the miRNA targets CERS1 (ceramide synthase 1), NAT8L (N-acetyltransferase 8-like [GCN5-related, putative]), and LARP1 (La ribonucleoprotein domain family, member 1). CERS1 and NAT8L participate in autophagy by affecting mitochondrial function. \u003ci\u003eTGFB2-OT1\u003c/i\u003e increased the LARP1 level, which promoted SQSTM1 (sequestosome 1) expression, NFKB RELA and CASP1 activation, and then production of IL6, IL8 and IL1B in VECs. Thus, NUPR1 and TIA1 may control the level of \u003ci\u003eTGFB2-OT1\u003c/i\u003e, and \u003ci\u003eTGFB2-OT1\u003c/i\u003e bound to \u003ci\u003eMIR3960, MIR4488\u003c/i\u003e and \u003ci\u003eMIR4459\u003c/i\u003e, which targeted CERS1, NAT8L, and LARP1, respectively, the key proteins involved in autophagy and inflammation.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeG1sbnM6eHNpPSJodHRwOi8vd3d3LnczLm9yZy8yMDAxL1hNTFNjaGVtYS1pbnN0YW5jZSIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00LjQvbWV0YWRhdGEueHNkIj4KICA8aWRlbnRpZmllciBpZGVudGlmaWVyVHlwZT0iRE9JIj4xMC42MDg0L005LkZJR1NIQVJFLkMuMjEyODMxNjwvaWRlbnRpZmllcj4KICA8Y3JlYXRvcnM+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlNodVlhIEh1YW5nPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5TaHVZYTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5IdWFuZzwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+V2VpIEx1PC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5XZWk8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+THU8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkRpIEdlPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5EaTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5HZTwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+TmluZyBNZW5nPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5OaW5nPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPk1lbmc8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPllpbmcgTGk8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPllpbmc8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+TGk8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkxlIFN1PC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5MZTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5TdTwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+U2hhbmdMaSBaaGFuZzwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+U2hhbmdMaTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5aaGFuZzwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+WXVuIFpoYW5nPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5ZdW48L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+Wmhhbmc8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkJhb1hpYW5nIFpoYW88L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkJhb1hpYW5nPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPlpoYW88L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkp1bllpbmcgTWlhbzwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+SnVuWWluZzwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5NaWFvPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogIDwvY3JlYXRvcnM+CiAgPHRpdGxlcz4KICAgIDx0aXRsZT5BIG5ldyBtaWNyb1JOQSBzaWduYWwgcGF0aHdheSByZWd1bGF0ZWQgYnkgbG9uZyBub25jb2RpbmcgUk5BIFRHRkIyLU9UMSBpbiBhdXRvcGhhZ3kgYW5kIGluZmxhbW1hdGlvbiBvZiB2YXNjdWxhciBlbmRvdGhlbGlhbCBjZWxsczwvdGl0bGU+CiAgPC90aXRsZXM+CiAgPGRlc2NyaXB0aW9ucz4KICAgIDxkZXNjcmlwdGlvbiBkZXNjcmlwdGlvblR5cGU9IkFic3RyYWN0Ij4mbHQ7cCZndDsmbHQ7aSZndDtUR0ZCMi1PVDEmbHQ7L2kmZ3Q7ICgmbHQ7aSZndDtUR0ZCMiZsdDsvaSZndDsgb3ZlcmxhcHBpbmcgdHJhbnNjcmlwdCAxKSBpcyBhIG5ld2x5IGRpc2NvdmVyZWQgbG9uZyBub25jb2RpbmcgUk5BIChsbmNSTkEpIGRlcml2ZWQgZnJvbSB0aGUgM+KAslVUUiBvZiBUR0ZCMi4gSXQgY2FuIHJlZ3VsYXRlIGF1dG9waGFneSBpbiB2YXNjdWxhciBlbmRvdGhlbGlhbCBjZWxscyAoVkVDcykuIEhvd2V2ZXIsIHRoZSBtZWNoYW5pc21zIG9mICZsdDtpJmd0O1RHRkIyLU9UMSZsdDsvaSZndDsgYWN0aW9uIGFyZSB1bmNsZWFyLCBhbmQgd2hldGhlciBpdCBpcyBpbnZvbHZlZCBpbiBWRUNzIGR5c2Z1bmN0aW9uIG5lZWRzIGludmVzdGlnYXRpb24uIEhlcmUsIHRoZSBsZXZlbCBvZiAmbHQ7aSZndDtUR0ZCMi1PVDEmbHQ7L2kmZ3Q7IHdhcyBtYXJrZWRseSBpbmNyZWFzZWQgYnkgbGlwb3BvbHlzYWNjaGFyaWRlIGFuZCBveGlkaXplZCBsb3ctZGVuc2l0eSBsaXBvcHJvdGVpbiwgMiBWRUNzIGluZmxhbW1hdGlvbiB0cmlnZ2Vycy4gQSBjaGVtaWNhbCBzbWFsbCBtb2xlY3VsZSwgMy1iZW56eWwtNS0oKDItbml0cm9waGVub3h5KSBtZXRoeWwpLWRpaHlkcm9mdXJhbi0yKDNIKS1vbmUgKDNCRE8pIHNpZ25pZmljYW50bHkgZGVjcmVhc2VkICZsdDtpJmd0O1RHRkIyLU9UMSZsdDsvaSZndDsgbGV2ZWxzIGFuZCBpbmhpYml0ZWQgdGhlIGVmZmVjdCBvZiBMUFMgYW5kIG94TERMLiBUaGUgTlVQUjEgbGV2ZWwgd2FzIHVwcmVndWxhdGVkIGJ5IHRoZSAyIGluZmxhbW1hdGlvbiBpbmR1Y2VycyBhbmQgbW9kdWxhdGVkIHRoZSAmbHQ7aSZndDtUR0ZCMi1PVDEmbHQ7L2kmZ3Q7IGxldmVsIGJ5IHByb21vdGluZyB0aGUgZXhwcmVzc2lvbiBvZiBUSUExLCByZXNwb25zaWJsZSBmb3IgJmx0O2kmZ3Q7VEdGQjItT1QxJmx0Oy9pJmd0OyBwcm9jZXNzaW5nLiBXZSBmb2N1c2VkIG9uIGhvdyAmbHQ7aSZndDtUR0ZCMi1PVDEmbHQ7L2kmZ3Q7IHJlZ3VsYXRlZCBhdXRvcGhhZ3kgYW5kIGluZmxhbW1hdGlvbi4gVXNlIG9mIG1pUk5BIGNoaXAgYXNzYXksICZsdDtpJmd0O1RHRkIyLU9UMSZsdDsvaSZndDsgb3ZlcmV4cHJlc3Npb24gdGVjaG5vbG9neSBhbmQgM0JETyByZXZlYWxlZCB0aGF0ICZsdDtpJmd0O1RHRkIyLU9UMSZsdDsvaSZndDsgcmVndWxhdGVkIHRoZSBsZXZlbHMgb2YgMyBtaWNyb1JOQXMsICZsdDtpJmd0O01JUjM5NjAsIE1JUjQ0ODgmbHQ7L2kmZ3Q7IGFuZCAmbHQ7aSZndDtNSVI0NDU5Jmx0Oy9pJmd0Oy4gRnVydGhlciBzdHVkaWVzIGNvbmZpcm1lZCB0aGF0ICZsdDtpJmd0O1RHRkIyLU9UMSZsdDsvaSZndDsgYWN0ZWQgYXMgYSBjb21wZXRpbmcgZW5kb2dlbm91cyBSTkEsIGJvdW5kIHRvICZsdDtpJmd0O01JUjM5NjAsIE1JUjQ0ODgmbHQ7L2kmZ3Q7IGFuZCAmbHQ7aSZndDtNSVI0NDU5Jmx0Oy9pJmd0OywgdGhlbiByZWd1bGF0ZWQgdGhlIGV4cHJlc3Npb24gb2YgdGhlIG1pUk5BIHRhcmdldHMgQ0VSUzEgKGNlcmFtaWRlIHN5bnRoYXNlIDEpLCBOQVQ4TCAoTi1hY2V0eWx0cmFuc2ZlcmFzZSA4LWxpa2UgW0dDTjUtcmVsYXRlZCwgcHV0YXRpdmVdKSwgYW5kIExBUlAxIChMYSByaWJvbnVjbGVvcHJvdGVpbiBkb21haW4gZmFtaWx5LCBtZW1iZXIgMSkuIENFUlMxIGFuZCBOQV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