title: MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2.
abstract: Osteosarcoma is the most common type of bone cancer, especially in children and young adults. Recently, long noncoding RNAs (lncRNAs) have emerged as new prognostic markers and gene regulators in several cancers, including osteosarcoma. In this study, we investigated the contributions of the lncRNA MALAT1 in osteosarcoma with a specific focus on its transcriptional regulation and its interaction with EZH2. Our results showed that MALAT1 was significantly increased in osteosarcoma specimens and cell lines. ROC curve analysis showed that MALAT1 had a higher area under the curve than alkaline phosphatase, and Kaplan-Meier survival analysis indicated that patients with high serum levels of MALAT1 showed reduced survival rate. Knockdown of MALAT1 decreased osteosarcoma cell invasion and promoted E-cadherin expression. Mechanistic investigations showed that MALAT1 was transcriptionally activated by TGF-β. Additionally, EZH2 is highly expressed and associated with the 3' end region of lncRNA MALAT1 in osteosarcoma, and this association finally suppressed the expression of E-cadherin. Subsequently, our gain and loss function assay showed that MALAT1 overexpression promoted cell metastasis and decreased E-cadherin level, however, this effect was partially reversed by EZH2 knockdown. In conclusion, our work illuminates that lncRNA MALAT1 is a potential diagnostic and prognostic factor in osteosarcoma and further demonstrates how MALAT1 confers an oncogenic function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.
authors.affiliation: Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huo
authors.affiliation: Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China.
authors.forename: Xiqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China.
authors.forename: Xiejia
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Health Management, The Second Hospital of Shandong University, Jinan, 250133, Shandong Province, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Pan
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D012372:ROC Curve; D016212:Transforming Growth Factor beta / Q000378:metabolism; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D015820:Cadherins; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D016212:Transforming Growth Factor beta; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: EZH2; MALAT1; TGF-β; metastasis; osteosarcoma