{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:42:10Z","timestamp":1792788130561,"version":"4.5.0"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"publisher","award":["81572517"],"award-info":[{"award-number":["81572517"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"national natural science foundation of china","doi-asserted-by":"publisher","award":["82070773"],"award-info":[{"award-number":["82070773"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"scientific research foundation of graduate school of southeast university","award":["YBPY2173"],"award-info":[{"award-number":["YBPY2173"]}]},{"name":"postgraduate research & practice innovation program of jiangsu province","award":["KYCX21_0156"],"award-info":[{"award-number":["KYCX21_0156"]}]},{"DOI":"10.13039\/501100013058","name":"jiangsu provincial key research and development program","doi-asserted-by":"publisher","award":["BE2019751"],"award-info":[{"award-number":["BE2019751"]}],"id":[{"id":"10.13039\/501100013058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005065","name":"innovative team of jiangsu province","doi-asserted-by":"publisher","award":["2017XKJQW07"],"award-info":[{"award-number":["2017XKJQW07"]}],"id":[{"id":"10.13039\/501100005065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the national key research and development program of china","award":["SQ2017YFSF090096"],"award-info":[{"award-number":["SQ2017YFSF090096"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE\/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a \"ceRNA\" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K\/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE\/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p\/TAGLN axis and activating the PI3K\/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE\/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.<\/jats:p>","DOI":"10.1186\/s12943-021-01443-2","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T01:02:35Z","timestamp":1636074155000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma"],"prefix":"10.1186","volume":"20","author":[{"given":"Weipu","family":"Mao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-6886","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"issue":"1","key":"1443_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","volume":"70","author":"RL Siegel","year":"2020","unstructured":"Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7\u201330.","journal-title":"CA Cancer J Clin"},{"issue":"4","key":"1443_CR2","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/S1470-2045(19)30024-5","volume":"20","author":"Y Lotan","year":"2019","unstructured":"Lotan Y, Margulis V. Predicting recurrence in patients with localised renal cell carcinoma after nephrectomy. Lancet Oncol. 2019;20(4):473\u20135.","journal-title":"Lancet Oncol"},{"issue":"3","key":"1443_CR3","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"CA Cancer J Clin"},{"issue":"10021","key":"1443_CR4","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/S0140-6736(15)00046-X","volume":"387","author":"U Capitanio","year":"2016","unstructured":"Capitanio U, Montorsi F. Renal cancer. Lancet. 2016;387(10021):894\u2013906.","journal-title":"Lancet."},{"issue":"9","key":"1443_CR5","doi-asserted-by":"publisher","first-page":"e1003777","DOI":"10.1371\/journal.pgen.1003777","volume":"9","author":"J Salzman","year":"2013","unstructured":"Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO. Cell-type specific features of circular RNA expression. PLoS Genet. 2013;9(9):e1003777.","journal-title":"PLoS Genet"},{"issue":"1","key":"1443_CR6","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12943-017-0663-2","volume":"16","author":"S Meng","year":"2017","unstructured":"Meng S, Zhou H, Feng Z, Xu Z, Tang Y, Li P, et al. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer. 2017;16(1):94.","journal-title":"Mol Cancer"},{"issue":"1","key":"1443_CR7","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/s13046-019-1136-9","volume":"38","author":"W Mao","year":"2019","unstructured":"Mao W, Huang X, Wang L, Zhang Z, Liu M, Li Y, et al. Circular RNA hsa_circ_0068871 regulates FGFR3 expression and activates STAT3 by targeting miR-181a-5p to promote bladder cancer progression. J Exp Clin Cancer Res. 2019;38(1):169.","journal-title":"J Exp Clin Cancer Res"},{"issue":"7573","key":"1443_CR8","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/nature15818","volume":"526","author":"L Naldini","year":"2015","unstructured":"Naldini L. Gene therapy returns to Centre stage. 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ACS Nano. 2015;9(2):1236\u201349.","journal-title":"ACS Nano"}],"updated-by":[{"DOI":"10.1186\/s12943-021-01459-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000}}],"container-title":["Molecular Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-021-01443-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12943-021-01443-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12943-021-01443-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T10:02:47Z","timestamp":1638525767000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecular-cancer.biomedcentral.com\/articles\/10.1186\/s12943-021-01443-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,5]]},"references-count":9,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1443"],"URL":"https:\/\/doi.org\/10.1186\/s12943-021-01443-2","relation":{},"ISSN":["1476-4598"],"issn-type":[{"value":"1476-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,5]]},"assertion":[{"value":"28 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s12943-021-01459-8","URL":"https:\/\/doi.org\/10.1186\/s12943-021-01459-8","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal experiments were conducted in mice using protocols approved by the Ethics Committee of Shanghai Tenth People\u2019s Hospital of Tongji University, and written informed consent was obtained from all patients or their relatives.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We have obtained consents to publish this paper from all the participants of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"142"}}