Long noncoding RNA MIAT promotes non-small cell lung cancer proliferation and metastasis through MMP9 activation
Autor: | Ya-Sian Chang, Ju-Chen Yen, Ya-Ting Lee, Pei-Chin Lin, Chin-An Yang, Jan-Gowth Chang, Wen-Ling Chan, I-Lu Lai |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Pathology mixed-lineage leukemia (MLL) non-small cell lung cancer (NSCLC) medicine.disease_cause Metastasis 03 medical and health sciences Prostate cancer 0302 clinical medicine Internal medicine medicine Lung cancer Hematology Oncogene business.industry long noncoding RNA (lncRNA) medicine.disease Long non-coding RNA MIAT 030104 developmental biology 030220 oncology & carcinogenesis matrix metallopeptidase 9 (MMP9) Carcinogenesis business Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | // I-Lu Lai 1, 8 , Chin-An Yang 2, 3, 4 , Pei-Chin Lin 5, 6, 7 , Wen-Ling Chan 1, 8 , Ya-Ting Lee 1 , Ju-Chen Yen 1 , Ya-Sian Chang 1, 2 and Jan-Gowth Chang 1, 2, 4 1 Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan 2 Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan 3 Division of General Pediatrics, Children’s Hospital of China Medical University, Taichung, Taiwan 4 College of Medicine, China Medical University, Taichung, Taiwan 5 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Department of Pediatrics, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Division of Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Department of Bioinformatics and Medical Enginerring, Asia University, Taichung, Taiwan Correspondence to: Ya-Sian Chang, email: t25074@mail.cmuh.org.tw Jan-Gowth Chang, email: d6781@mail.cmuh.org.tw Keywords: MIAT, long noncoding RNA (lncRNA), non-small cell lung cancer (NSCLC), mixed-lineage leukemia (MLL), matrix metallopeptidase 9 (MMP9) Received: March 31, 2017 Accepted: August 17, 2017 Published: October 03, 2017 ABSTRACT Long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis. Myocardial infarction-associated transcript (MIAT), originally isolated as a candidate gene for myocardial infarction, has been found to act as an oncogene in chronic lymphocytic leukaemias and neuroendocrine prostate cancer (NEPC); however, little is known about its expression pattern, biological function, and underlying mechanism in non-small cell lung cancer (NSCLC). In this study, we observed that MIAT expression was upregulated in NSCLC, and its overexpression was associated with advanced tumor stage. Moreover, MIAT knockdown decreased cell proliferation, migration, invasion, and cell cycle arrested in G1 phase. Mechanistic investigation revealed that MIAT could interact with histone methyltransferase mixed-lineage leukemia (MLL). MIAT silencing impeded the binding of MLL on the matrix metalloproteinase 9 (MMP9) promoter region and epigenetically reduced MMP9 transcriptional activity. Overall, our findings suggest that MIAT expression is associated with NSCLC and may be one of the critical targets in progression and metastasis in NSCLC. |
Databáze: | OpenAIRE |
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