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However, its molecular pathogenesis is poorly understood. HMGA2\u2010ULM is the second major subtype of human ULM and associates with large sizes, fast\u2010growth, and high percentages of estrogen receptor \u03b1 (ER\u03b1). As altered ER\u03b1 expression plays a distinct role in ULM growth, here, we investigate a regulatory mechanism driving ULM growth via HMGA2 and ER\u03b1. We reveal a positive correlation of HMGA2 with ER\u03b1 protein and demonstrate that HMGA2 promotes ULM cells proliferation via ER\u03b1. In addition, autophagy pathway and p62\/SQSTM1 (a selective autophagy receptor) are found to participate in the regulation of HMGA2 and ER\u03b1. Moreover, HMGA2 suppresses the transcription of p62 by binding to its promoter, meanwhile, p62 interacts with ER\u03b1, and inhibition of p62 increases ER\u03b1 expression and enhances cell viability in ULM, suggesting a novel mechanism of the HMGA2\u2010p62\u2010ER\u03b1 axis in ULM proliferation. Notably, rapamycin, a familiar autophagy agonist, reduces ER\u03b1 levels and the proliferation ability of ULM cells. This study demonstrates a causal role of the HMGA2\u2010p62\u2010ER\u03b1 axis in preventing autophagy and increasing ER\u03b1 expression in HMGA2\u2010ULM. Therefore, blocking HMGA2\u2010p62\u2010ER\u03b1 axis and targeting autophagy pathway establish a roadmap toward HMGA2\u2010ULM medical treatment.<\/jats:p>","DOI":"10.1096\/fj.202000520r","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T14:13:38Z","timestamp":1596032018000},"page":"10966-10983","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["An HMGA2\u2010p62\u2010ER\u03b1 axis regulates uterine leiomyomas proliferation"],"prefix":"10.1096","volume":"34","author":[{"given":"Binya","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gynecology of Shanghai First Maternity and Infant Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofang","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research Center of Shanghai First Maternity and Infant 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