title: Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer.
abstract: Brain metastasis often has a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC). Therefore, it is urgent to identify factors associated with lung cancer brain metastasis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) also known as noncoding nuclear-enriched abundant transcript 2 is a long noncoding RNA, which is highly conserved amongst mammals. It has been shown to be increased in a variety of tumors including NSCLC and regulate the expression of metastasis-associated genes. However, the role of MALAT1 in lung cancer brain metastasis has not been investigated. In this study, we examined the level of MALAT1 in 78 cases of NSCLC samples with 19 brain metastasis and 59 non-brain metastasis by qRT-PCR. We observed that the level of MALAT1 was significantly higher in brain metastasis than that of non brain metastasis samples (P < 0.001). The level of MALAT1 was associated with patients' survival. To investigate the role of MALAT1 in brain metastasis, we established a highly invasive and metastatic cell subline using the brain metastasis lung cancer cell H1915. We found that MALAT1 is increased in highly invasive subline of brain metastasis lung cancer cells. Further functional studies indicate that silencing MALAT1 inhibits highly invasive subline of brain metastasis lung cancer cell migration and metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, increased level of long noncoding RNA MALAT1 promotes lung cancer brain metastasis by inducing EMT, which may be a promising prognosis factor and therapeutic target to treat lung cancer brain metastasis in future.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Jiang
authors.forename: Hongping
authors.initials: H
authors.lastname: Xia
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000503:physiopathology* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding