title: miR-145, targeting high-mobility group A2, is a powerful predictor of patient outcome in ovarian carcinoma.
abstract: MicroRNA-145 (miR-145) expression is downregulated in several human cancers, but its clinical and functional relevance to ovarian carcinoma has not yet been elucidated. This study addressed the hypothesis that miR-145 serves as a prognostic biomarker and a tumor suppressor that regulates the expression of high-mobility group A2 (HMGA2) oncoprotein in ovarian cancer. Here, we found that low miR-145 expression and HMGA2 overexpression determined by qRT-PCR and immunohistochemistry significantly correlated with advanced stage, lymph node involvement, and distant metastasis in 74 ovarian carcinomas. Low miR-145 expression significantly correlated with tumor recurrence and worse overall survival (HR=8.62, P = 0.039). Transfection of pre-miR-145 resulted in reduced cell growth and migration, and increased apoptosis of ovarian cancer cells by TUNEL, colony forming, and cell migration assays. MiR-145 was found to directly target HMGA2 by luciferase assay and Western blotting. Our findings suggest that miR-145 functions as a tumor suppressor in ovarian cancer and directly targets HMGA2 oncoprotein. Low miR-145 and high HMGA2 expressions are potential biomarkers of poor prognosis of ovarian carcinoma and miR-145 is the more powerful predictor of patient outcome.
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: Tae Hoen
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Song
authors.affiliation: Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea; Department of Gynecologic Oncology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
authors.affiliation: Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Jeong
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: A-Young
authors.initials: AY
authors.lastname: Kwon
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Heo
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: Haeyoun
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
authors.forename: Gwangil
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea. Electronic address: hjahn@cha.ac.kr.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: An
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D014945:Wound Healing
chemical_list: D025743:HMGA2 Protein; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: HMGA2; MicroRNA-145; Ovarian carcinoma; Prognosis; Survival