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Cbl proto\u2010oncogene like 1 (CBLL1) is an E3 ubiquitin ligase, which has been reported to vary with the menstrual cycle in the endometrium. However, whether CBLL1 is involved in the occurrence and development of RSA remains unclear. This study aimed to investigate the effects of CBLL1 on RSA. We analyzed the expression of CBLL1 in the decidua of RSA patients, as well as its functional effects on cellular senescence, oxidative stress, and proliferation of human endometrial stromal cells (HESCs). RNA sequencing was employed to identify a key downstream target gene regulated by CBLL1. We found that CBLL1 was upregulated in the decidua of RSA patients. Additionally, overexpression of CBLL1 promoted HESC senescence, increased oxidative stress levels, and inhibited proliferation. Phosphatase and tensin homolog located on chromosome 10 (PTEN) was identified as one of the important downstream target genes of CBLL1. In\u00a0vivo experiments demonstrated that CBLL1 overexpression in the endometrium caused higher embryo absorption rate in mice. Consequently, elevated CBLL1 expression is a potential cause of RSA, representing a novel therapeutic target for RSA.<\/jats:p>","DOI":"10.1096\/fj.202400972r","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T11:30:31Z","timestamp":1721129431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>CBLL1<\/scp>\n                    promotes endometrial stromal cell senescence via inhibiting\n                    <scp>PTEN<\/scp>\n                    in recurrent spontaneous abortion"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7489-0339","authenticated-orcid":false,"given":"Xueqing","family":"Liu","sequence":"first","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  Shanghai 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