title: HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes.
abstract: The AT-hook transcription factor HMGA2 is an oncogene involved in the tumorigenesis of many malignant neoplasms. HMGA2 overexpression is common in both early and late-stage high-grade ovarian serous papillary carcinoma. To test whether HMGA2 participates in the initiation of ovarian cancer and promotion of aggressive tumor growth, we examined the oncogenic properties of HMGA2 in ovarian surface epithelial (OSE) cell lines. We found that introduction of HMGA2 overexpression was sufficient to induce OSE transformation in vitro. HMGA2-mediated OSE transformation resulted in tumor formation in the xenografts of nude mice. By silencing HMGA2 in HMGA2-overexpressing OSE and ovarian cancer cell lines, the aggressiveness of tumor cell growth behaviors was partially suppressed. Global gene profiling analyses revealed that HMGA2-mediated tumorigenesis was associated with expression changes of target genes and microRNAs that are involved in epithelial-to-mesenchymal transition (EMT). Lumican, a tumor suppressor that inhibits EMT, was found to be transcriptionally repressed by HMGA2 and was frequently lost in human high-grade serous papillary carcinoma. Our findings show that HMGA2 overexpression confers a powerful oncogenic signal in ovarian cancers through the modulation of EMT genes.
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education, Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.forename: Zhaojian
authors.initials: Z
authors.lastname: Liu
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
authors.forename: Eva
authors.initials: E
authors.lastname: Hernando
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.forename: Masashi
authors.initials: M
authors.lastname: Narita
authors.forename: William
authors.initials: W
authors.lastname: Muller
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wei
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D018283:Cystadenocarcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D025743:HMGA2 Protein / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007632:Keratan Sulfate / Q000096:biosynthesis / Q000235:genetics; D000071234:Lumican; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D025743:HMGA2 Protein; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; D034741:RNA, Small Interfering; D007632:Keratan Sulfate