MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway

被引:299
作者
Dong, Yongqiang [1 ]
Liang, Guojun [1 ]
Yuan, Bo [1 ]
Yang, Chaoqun [2 ]
Gao, Rui [2 ]
Zhou, Xuhui [2 ]
机构
[1] Xinchang Cty Peoples Hosp, Dept Spine Surg, Shaoxing 312500, Zhejiang, Peoples R China
[2] Second Mil Med Univ, Changzheng Hosp, Dept Orthoped Surg, Shanghai 200003, Peoples R China
关键词
MALAT1; Osteosarcoma; Growth; Migration; NONCODING RNA; CANCER; INHIBITION; APOPTOSIS; SURVIVAL; GENOME;
D O I
10.1007/s13277-014-2631-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), one of the first found cancer-associated long noncoding RNAs (lncRNAs), involves in the development and progression of many types of tumors. An aberrant expression of MALAT1 was observed in hepatocellular carcinoma, cervical cancer, breast cancer, ovarian cancer, and colorectal cancer. However, the exact effects and molecular mechanisms of MALAT1 in osteosarcoma progression are still unknown up to now. Here, we investigated the role of MALAT1 in human osteosarcoma cell lines and clinical tumor samples in order to determine the function of this molecule. In our research, the MALAT1 messenger RNA (mRNA) was highly expressed in human osteosarcoma tissues, and its expression level was closely correlated with pulmonary metastasis. Then, we employed lentivirus-mediated knockdown of MALAT1 in U-2 OS and SaO2 to determine the role of MALAT1 in osteosarcoma cell lines. Lentivirus-mediated MALAT1 small interfering RNA (siRNA) could efficiently downregulated the expression level of MALAT1 in osteosarcoma cell lines. Knockdown of MALAT1 inhibited the proliferation and invasion of human osteosarcoma cell and suppressed its metastasis in vitro and vivo. At the same time, the proliferating cell nuclear antigen (PCNA), matrix metallopeptidase 9 (MMP-9), phosphorylated PI3Kp85 alpha, and Akt expressions were significantly inhibited in MALAT1-deleted cells. These findings indicated that MALAT1 might suppress the tumor growth and metastasis via PI3K/AKT signaling pathway. Taken together, our data indicated that MALAT1 might be an oncogenic lncRNA that promoted proliferation and metastasis of osteosarcoma and could be regarded as a therapeutic target in human osteosarcoma.
引用
收藏
页码:1477 / 1486
页数:10
相关论文
共 29 条
[1]   Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project [J].
Birney, Ewan ;
Stamatoyannopoulos, John A. ;
Dutta, Anindya ;
Guigo, Roderic ;
Gingeras, Thomas R. ;
Margulies, Elliott H. ;
Weng, Zhiping ;
Snyder, Michael ;
Dermitzakis, Emmanouil T. ;
Stamatoyannopoulos, John A. ;
Thurman, Robert E. ;
Kuehn, Michael S. ;
Taylor, Christopher M. ;
Neph, Shane ;
Koch, Christoph M. ;
Asthana, Saurabh ;
Malhotra, Ankit ;
Adzhubei, Ivan ;
Greenbaum, Jason A. ;
Andrews, Robert M. ;
Flicek, Paul ;
Boyle, Patrick J. ;
Cao, Hua ;
Carter, Nigel P. ;
Clelland, Gayle K. ;
Davis, Sean ;
Day, Nathan ;
Dhami, Pawandeep ;
Dillon, Shane C. ;
Dorschner, Michael O. ;
Fiegler, Heike ;
Giresi, Paul G. ;
Goldy, Jeff ;
Hawrylycz, Michael ;
Haydock, Andrew ;
Humbert, Richard ;
James, Keith D. ;
Johnson, Brett E. ;
Johnson, Ericka M. ;
Frum, Tristan T. ;
Rosenzweig, Elizabeth R. ;
Karnani, Neerja ;
Lee, Kirsten ;
Lefebvre, Gregory C. ;
Navas, Patrick A. ;
Neri, Fidencio ;
Parker, Stephen C. J. ;
Sabo, Peter J. ;
Sandstrom, Richard ;
Shafer, Anthony .
NATURE, 2007, 447 (7146) :799-816
[2]  
BRAUZE D, 1990, ACTA BIOCHIM POL, V37, P219
[3]   A review of clinical and molecular prognostic factors in osteosarcoma [J].
Clark, Jonathan C. M. ;
Dass, Crispin R. ;
Choong, Peter F. M. .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2008, 134 (03) :281-297
[4]  
EDMONDSON HA, 1954, CANCER-AM CANCER SOC, V7, P462, DOI 10.1002/1097-0142(195405)7:3<462::AID-CNCR2820070308>3.0.CO
[5]  
2-E
[6]   Prognostic significance of drug-regulated genes in high-grade osteosarcoma [J].
Fellenberg, Joerg ;
Bernd, Ludger ;
Delling, Guenter ;
Witte, Daniela ;
Zahlten-Hinguranage, Anita .
MODERN PATHOLOGY, 2007, 20 (10) :1085-1094
[7]  
Feng J., 2012, HEAD NECK ONCOL, V4, P46
[8]   Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis [J].
Gupta, Rajnish A. ;
Shah, Nilay ;
Wang, Kevin C. ;
Kim, Jeewon ;
Horlings, Hugo M. ;
Wong, David J. ;
Tsai, Miao-Chih ;
Hung, Tiffany ;
Argani, Pedram ;
Rinn, John L. ;
Wang, Yulei ;
Brzoska, Pius ;
Kong, Benjamin ;
Li, Rui ;
West, Robert B. ;
van de Vijver, Marc J. ;
Sukumar, Saraswati ;
Chang, Howard Y. .
NATURE, 2010, 464 (7291) :1071-U148
[9]   MALAT1- a paradigm for long noncoding RNA function in cancer [J].
Gutschner, Tony ;
Haemmerle, Monika ;
Diederichs, Sven .
JOURNAL OF MOLECULAR MEDICINE-JMM, 2013, 91 (07) :791-801
[10]   The hallmarks of cancer A long non-coding RNA point of view [J].
Gutschner, Tony ;
Diederichs, Sven .
RNA BIOLOGY, 2012, 9 (06) :703-719