Disrupting MALAT1/miR-200c sponge decreases invasion and migration in endometrioid endometrial carcinoma.
Endometrioid endometrial carcinoma (EEC) is the most common gynecologic malignancy around the world. Epithelial-to-mesenchymal transition (EMT) is a core process during EEC cell invasion. The abnormal expression of the long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) or miR-200 family members were shown to facilitate EMT in multiple human cancers, but the regulatory mechanism by which MALAT1 and miR-200 act remains unknown. Previous studies have shown that miR-200 family members are enriched in EEC as well as melanoma and some ovarian carcinomas. In the present study, we first showed that miR-200c levels were higher in most EEC specimens than in non-tumor tissues, while MALAT1 levels were lower. Moreover, we found that miR-200c bound directly to MALAT1 using luciferase reporter and qRT-PCR assays. MALAT1 and miR-200c are reciprocally repressed, and TGF-β increased MALAT1 expression by inhibiting miR-200c. When the interaction between miR-200c/MALAT1 was interrupted, the invasive capacity of EEC cells was decreased and EMT markers expression were altered in vitro. A xenograft tumor model was used to show that targeting the miR-200c/MALAT1 axis inhibited EEC growth and EMT-associated protein expression in vivo. In summary, miR-200c/MALAT1 axis is a target with therapeutic potential in EEC. However, different expression model of miR-200c and MALAT1 in EEC with that in other organ carcinomas needs further mechanism researches.
Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China; Key Laboratory of Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China; Department of Obstetrics and gynecology, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China.
Qiulian
Q
Li
Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
Chao
C
Zhang
Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Ruichao
R
Chen
Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Hanzhen
H
Xiong
Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Fuman
F
Qiu
Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Shaoyan
S
Liu
Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Minfen
M
Zhang
Key Laboratory of Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Fang
F
Wang
Department of Genitourinary Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
Yu
Y
Wang
Maxillary Facial and Otorhinolaryngology Head & Neck Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Xuan
X
Zhou
Key Laboratory of Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China. Electronic address: xiaogh66@163.com.
Guohong
G
Xiao
Maxillary Facial and Otorhinolaryngology Head & Neck Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: wxd.1133@163.com.
Xudong
X
Wang
Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China; Key Laboratory of Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China. Electronic address: Jiangqp2003@126.com.
Qingping
Q
Jiang
D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D047368:Tumor Burden
D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C557041:MALAT1 long non-coding RNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D016212:Transforming Growth Factor beta
Endometrioid endometrial carcinoma; Invasion; MALAT1; miR-200c