Regulation of MALAT1 expression by TDP43 controls the migration and invasion of non-small cell lung cancer cells in vitro.
MALAT1 is a non-coding RNA overexpressed in non-small cell lung cancer (NSCLC). TDP-43 is a ubiquitously expressed, MALAT1-binding protein implicated in cancer development. We hypothesized that MALAT1 expression level is regulated in lung cancer by TDP-43. We analyzed their functions in cultured NSCLC cells. Downregulation of MALAT1 or TDP-43 expression by siRNA not only markedly suppressed NSCLC cell growth, as measured by the MTT assay in vitro cultured NSCLC cells (P < 0.05), but also noticeably impaired the migration and invasion of NSCLC cells, as analyzed by the migration and invasion assay. We also confirm that TDP-43 directly bound to MALAT1 RNA by a RNA immunoprecipitation (RIP) assay and by luciferase reporter activity assay. In a RT-PCR assay, silencing TDP-43 expression effectively decreased MALAT1 RNA transcript level. In contrast, TDP-43 overexpression markedly increased MALAT1 transcript level. In summary, these findings demonstrated that MALAT1 expression by regulation of TDP-43 controls cellular growth, migration, and invasion of NSCLCs.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China.
Fengjie
F
Guo
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China.
Feng
F
Jiao
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China.
Zuoqing
Z
Song
The Second Hospital, Hebei Medical University, 215 Heping West Road, Shijiazhuang 050000, Hebei, PR China.
Shujun
S
Li
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China.
Bin
B
Liu
Geriatric Ward of Neurology, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China.
Hongwei
H
Yang
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China; Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China. Electronic address: zhouqh1016@yahoo.com.cn.
Qinghua
Q
Zhou
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China; Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin 300052, PR China. Electronic address: zhigli38@hotmail.com.
Zhigang
Z
Li
D001483:Base Sequence; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D004268:DNA-Binding Proteins; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000598624:TARDBP protein, human; D008156:Luciferases
Cellular migration and invasion; MALAT1; Non-small cell lung cancer; TDP-43