Skip to main content
Top
Published in: Tumor Biology 3/2015

01-03-2015 | Research Article

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

Authors: Yongqiang Dong, Guojun Liang, Bo Yuan, Chaoqun Yang, Rui Gao, Xuhui Zhou

Published in: Tumor Biology | Issue 3/2015

Login to get access

Abstract

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.
Literature
1.
go back to reference Huang J, Ni J, Liu K, Yu Y, Xie M, Kang R, et al. HMGB1 promotes drug resistance in osteosarcoma. Cancer Res. 2012;72:230–8.CrossRefPubMed Huang J, Ni J, Liu K, Yu Y, Xie M, Kang R, et al. HMGB1 promotes drug resistance in osteosarcoma. Cancer Res. 2012;72:230–8.CrossRefPubMed
2.
go back to reference Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008;134:281–97.CrossRefPubMed Clark JC, Dass CR, Choong PF. A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008;134:281–97.CrossRefPubMed
3.
go back to reference Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival—a report from the Children’s Oncology Group. J Clin Oncol. 2008;26:633–8.CrossRefPubMed Meyers PA, Schwartz CL, Krailo MD, Healey JH, Bernstein ML, Betcher D, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival—a report from the Children’s Oncology Group. J Clin Oncol. 2008;26:633–8.CrossRefPubMed
4.
6.
go back to reference Gutschner T, Hammerle M, Diederichs S. MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl). 2013;91:791–801.CrossRef Gutschner T, Hammerle M, Diederichs S. MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med (Berl). 2013;91:791–801.CrossRef
7.
go back to reference Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031–41.CrossRefPubMed Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031–41.CrossRefPubMed
8.
go back to reference Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, et al. Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci. 2006;97:106–12.CrossRefPubMed Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, et al. Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci. 2006;97:106–12.CrossRefPubMed
9.
go back to reference Brauze D, Mikstacka R, Pelkonen O. Monoclonal antibody characterization of NADH- and NADPH-dependent hydroxylation of benzo(a)pyrene in liver microsomes from 5,6-benzoflavone-induced C57Bl/6 mice. Acta Biochim Pol. 1990;37:219–25.PubMed Brauze D, Mikstacka R, Pelkonen O. Monoclonal antibody characterization of NADH- and NADPH-dependent hydroxylation of benzo(a)pyrene in liver microsomes from 5,6-benzoflavone-induced C57Bl/6 mice. Acta Biochim Pol. 1990;37:219–25.PubMed
10.
go back to reference Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007;26:851–8.CrossRefPubMed Lin R, Maeda S, Liu C, Karin M, Edgington TS. A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene. 2007;26:851–8.CrossRefPubMed
11.
go back to reference Feng J, Tian L, Sun Y, Li D, Wu T, Wang Y, et al. Expression of long non-coding ribonucleic acid metastasis-associated lung adenocarcinoma transcript-1 is correlated with progress and apoptosis of laryngeal squamous cell carcinoma. Head Neck Oncol. 2012;4:46. Feng J, Tian L, Sun Y, Li D, Wu T, Wang Y, et al. Expression of long non-coding ribonucleic acid metastasis-associated lung adenocarcinoma transcript-1 is correlated with progress and apoptosis of laryngeal squamous cell carcinoma. Head Neck Oncol. 2012;4:46.
12.
go back to reference Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y, et al. Expression profile of microRNAs in c-Myc induced mouse mammary tumors. Breast Cancer Res Treat. 2009;118:185–96.CrossRefPubMed Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y, et al. Expression profile of microRNAs in c-Myc induced mouse mammary tumors. Breast Cancer Res Treat. 2009;118:185–96.CrossRefPubMed
13.
go back to reference Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics. 2007;8:39.CrossRefPubMedPubMedCentral Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics. 2007;8:39.CrossRefPubMedPubMedCentral
14.
go back to reference Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentral Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentral
15.
go back to reference Ji Q, Zhang L, Liu X, Zhou L, Wang W, Han Z, et al. Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. Br J Cancer. 2014;111:736–48.CrossRefPubMedPubMedCentral Ji Q, Zhang L, Liu X, Zhou L, Wang W, Han Z, et al. Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. Br J Cancer. 2014;111:736–48.CrossRefPubMedPubMedCentral
16.
go back to reference Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, et al. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol. 2012;29:1810–6.CrossRefPubMed Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, et al. Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol. 2012;29:1810–6.CrossRefPubMed
17.
go back to reference Ying L, Chen Q, Wang Y, Zhou Z, Huang Y, Qiu F. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst. 2012;8:2289–94.CrossRefPubMed Ying L, Chen Q, Wang Y, Zhou Z, Huang Y, Qiu F. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst. 2012;8:2289–94.CrossRefPubMed
18.
go back to reference Taniguchi M, Fujiwara K, Nakai Y, Ozaki T, Koshikawa N, Toshio K, et al. Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif. FEBS Open Bio. 2014;4:328–34.CrossRefPubMedPubMedCentral Taniguchi M, Fujiwara K, Nakai Y, Ozaki T, Koshikawa N, Toshio K, et al. Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif. FEBS Open Bio. 2014;4:328–34.CrossRefPubMedPubMedCentral
20.
go back to reference Fellenberg J, Bernd L, Delling G, Witte D, Zahlten-Hinguranage A. Prognostic significance of drug-regulated genes in high-grade osteosarcoma. Mod Pathol. 2007;20:1085–94.CrossRefPubMed Fellenberg J, Bernd L, Delling G, Witte D, Zahlten-Hinguranage A. Prognostic significance of drug-regulated genes in high-grade osteosarcoma. Mod Pathol. 2007;20:1085–94.CrossRefPubMed
21.
go back to reference Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMed Edmondson HA, Steiner PE. Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. Cancer. 1954;7:462–503.CrossRefPubMed
22.
go back to reference Hong SK, Yoon S, Moelling C, Arthan D, Park JI. Noncatalytic function of ERK1/2 can promote Raf/MEK/ERK-mediated growth arrest signaling. J Biol Chem. 2009;284:33006–18.CrossRefPubMedPubMedCentral Hong SK, Yoon S, Moelling C, Arthan D, Park JI. Noncatalytic function of ERK1/2 can promote Raf/MEK/ERK-mediated growth arrest signaling. J Biol Chem. 2009;284:33006–18.CrossRefPubMedPubMedCentral
23.
go back to reference Zhang Y, Sun S, Chen J, Ren P, Hu Y, Cao Z, et al. Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma MNNG/HOS cells through inhibition of PI3K/Akt pathway. Tumour Biol. 2014;35:1619–25.CrossRefPubMed Zhang Y, Sun S, Chen J, Ren P, Hu Y, Cao Z, et al. Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma MNNG/HOS cells through inhibition of PI3K/Akt pathway. Tumour Biol. 2014;35:1619–25.CrossRefPubMed
24.
go back to reference Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, et al. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology. 2012;56:2231–41.CrossRefPubMed Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, et al. Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology. 2012;56:2231–41.CrossRefPubMed
25.
go back to reference Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, et al. Identification and analysis of functional elements in 1 % of the human genome by the encode pilot project. Nature. 2007;447:799–816.CrossRefPubMed Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, et al. Identification and analysis of functional elements in 1 % of the human genome by the encode pilot project. Nature. 2007;447:799–816.CrossRefPubMed
26.
go back to reference Wu XS, Wang XA, Wu WG, Hu YP, Li ML, Ding Q, et al. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther. 2014;15:806–14.CrossRefPubMedPubMedCentral Wu XS, Wang XA, Wu WG, Hu YP, Li ML, Ding Q, et al. MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway. Cancer Biol Ther. 2014;15:806–14.CrossRefPubMedPubMedCentral
27.
go back to reference Jin S, Pang RP, Shen JN, Huang G, Wang J, Zhou JG. Grifolin induces apoptosis via inhibition of PI3K/AKT signalling pathway in human osteosarcoma cells. Apoptosis. 2007;12:1317–26.CrossRefPubMed Jin S, Pang RP, Shen JN, Huang G, Wang J, Zhou JG. Grifolin induces apoptosis via inhibition of PI3K/AKT signalling pathway in human osteosarcoma cells. Apoptosis. 2007;12:1317–26.CrossRefPubMed
28.
go back to reference Liu B, Shi ZL, Feng J, Tao HM. Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. Cell Biol Int. 2008;32:494–501.CrossRefPubMed Liu B, Shi ZL, Feng J, Tao HM. Celecoxib, a cyclooxygenase-2 inhibitor, induces apoptosis in human osteosarcoma cell line MG-63 via down-regulation of PI3K/Akt. Cell Biol Int. 2008;32:494–501.CrossRefPubMed
Metadata
Title
MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway
Authors
Yongqiang Dong
Guojun Liang
Bo Yuan
Chaoqun Yang
Rui Gao
Xuhui Zhou
Publication date
01-03-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2631-4

Other articles of this Issue 3/2015

Tumor Biology 3/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine