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

马拉特1 骨肉瘤 癌症研究 转移 PI3K/AKT/mTOR通路 基因敲除 细胞生长 蛋白激酶B 生物 腺癌 增殖细胞核抗原 癌症 细胞培养 长非编码RNA 信号转导 核糖核酸 细胞生物学 基因 生物化学 遗传学
作者
Yongqiang Dong,Guojun Liang,Bo Yuan,Chaoqun Yang,Rui Gao,Xuhui Zhou
出处
期刊:Tumor Biology [SAGE]
卷期号:36 (3): 1477-1486 被引量:294
标识
DOI:10.1007/s13277-014-2631-4
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 PI3Kp85α, 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.
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