title: MALAT1 promotes colorectal cancer cell proliferation/migration/invasion via PRKA kinase anchor protein 9.
abstract: Our previous studies have shown that the 3' end of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is involved in colorectal cancer (CRC) cell proliferation and migration/invasion in vitro. The role and mechanism of MALAT1 in CRC metastasis in vivo, however, remain largely unknown. In the present study, we found that MALAT1 was up-regulated in human primary CRC tissues with lymph node metastasis. Overexpression of MALAT1 via RNA activation promoted CRC cell proliferation, invasion and migration in vitro, and stimulated tumor growth and metastasis in mice in vivo. Conversely, knockdown of MALAT1 inhibited CRC tumor growth and metastasis. MALAT1 regulated at least 243 genes in CRC cells in a genome-wide expression profiling. Among these genes, PRKA kinase anchor protein 9 (AKAP-9) was significantly up-regulated at both mRNA and protein levels. AKAP-9 was highly expressed in CRC cells with metastatic potential and human primary CRC tissues with lymph node metastasis, but not in normal cells or tissues. Importantly, knockdown of AKAP-9 blocked MALAT1-mediated CRC cell proliferation, migration and invasion. These data indicate that MALAT1 may promote CRC tumor development via its target protein AKAP-9.
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, China; Key Laboratory of Transcriptome and Proteome for Human Major Diseases of the Ministry of Education and Guangdong Province, Guangzhou 510515, Guangdong Province, China.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, China; Key Laboratory of Transcriptome and Proteome for Human Major Diseases of the Ministry of Education and Guangdong Province, Guangzhou 510515, Guangdong Province, China.
authors.forename: Zhi-Yan
authors.initials: ZY
authors.lastname: Hu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, China; Key Laboratory of Transcriptome and Proteome for Human Major Diseases of the Ministry of Education and Guangdong Province, Guangzhou 510515, Guangdong Province, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, China; Key Laboratory of Transcriptome and Proteome for Human Major Diseases of the Ministry of Education and Guangdong Province, Guangzhou 510515, Guangdong Province, China.
authors.forename: Lin-Ying
authors.initials: LY
authors.lastname: Xie
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, China; Key Laboratory of Transcriptome and Proteome for Human Major Diseases of the Ministry of Education and Guangdong Province, Guangzhou 510515, Guangdong Province, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Physiology & Pharmacology, University of Georgia, Athens, GA, USA. Electronic address: sc229@uga.edu.
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, China; Key Laboratory of Transcriptome and Proteome for Human Major Diseases of the Ministry of Education and Guangdong Province, Guangzhou 510515, Guangdong Province, China. Electronic address: Lizg@smu.edu.cn.
authors.forename: Zu-Guo
authors.initials: ZG
authors.lastname: Li
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D062085:RNA, Long Noncoding / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D003598:Cytoskeletal Proteins; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding
keywords: Colorectal cancer; Long non-coding RNA; Metastasis; Metastasis associated lung adenocarcinoma transcript 1; PRKA kinase anchor protein 9