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However, the molecular mechanisms of lncRNAs in cancer are not fully understood. Our study describes the role of the lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) in cancer metastasis by mechanisms related to Staufen1 (STAU1)-mediated mRNA decay (SMD). Briefly, we found that, high SPRY4-IT1 expression was associated with aggressiveness and poor outcome in human colorectal, breast and ovarian cancer tissues. In addition, functional assays revealed that SPRY4-IT1 significantly promoted colorectal, breast and ovarian cancer metastasis in vitro and in vivo. Mechanistically, microarray analyses identified several differentially-expressed genes upon SPRY4-IT1 overexpression in HCT 116 colorectal cancer cells. Among them, the 3\u2032-UTR of transcription elongation factor B subunit 1 (<jats:italic>TCEB1<\/jats:italic>) mRNA can base-pair with the Alu element in the 3\u2032-UTR of SPRY4-IT1. Moreover, SPRY4-IT1 was found to bind STAU1, promote STAU1 recruitment to the 3\u2032-UTR of <jats:italic>TCEB1<\/jats:italic> mRNA, and affect <jats:italic>TCEB1<\/jats:italic> mRNA stability and expression, resulting in hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) upregulation, and thereby affecting cancer cell metastasis. In addition, STAU1 depletion abrogated <jats:italic>TCEB1<\/jats:italic> SMD and alleviated the pro-metastatic effect of SPRY4-IT1 overexpression. Significantly, we revealed that SPRY4-IT1 is also transactivated by NF-\u03baB\/p65, which activates SPRY4-IT1 to inhibit <jats:italic>TCEB1<\/jats:italic> expression, and subsequently upregulate HIF-1\u03b1. In conclusion, our results highlight a novel mechanism of cytoplasmic lncRNA SPRY4-IT1 in which SPRY4-IT1 affecting <jats:italic>TCEB1<\/jats:italic> mRNA stability via STAU1-mediated degradation during cancer metastasis.<\/jats:p>","DOI":"10.1038\/s41388-021-01900-8","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T18:03:57Z","timestamp":1624471437000},"page":"4919-4929","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["NF-\u03baB-activated SPRY4-IT1 promotes cancer cell metastasis by downregulating TCEB1 mRNA via Staufen1-mediated mRNA decay"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-6455","authenticated-orcid":false,"given":"Lin","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longyang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiutong","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-2764","authenticated-orcid":false,"given":"Jingdong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0404-7098","authenticated-orcid":false,"given":"Minjie","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"1900_CR1","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1126\/science.1203543","volume":"331","author":"CL Chaffer","year":"2011","unstructured":"Chaffer CL, Weinberg RA. 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