LncRNA LOXL1-AS1 Promotes the Proliferation and Metastasis of Medulloblastoma by Activating the PI3K/AKT Pathway

被引：71

作者：

Gao, Ran ^{[1
]}

Zhang, Rui ^{[2
]}

Zhang, Cuicui ^{[3
]}

Liang, Yingwu ^{[1
]}

Tang, Weining ^{[1
]}

机构：

[1] Jining 1 Peoples Hosp, Dept Pediat, Jining, Shandong, Peoples R China

[2] Sishui Peoples Hosp, Dept Pediat, Sishui, Shandong, Peoples R China

[3] Jining Med Univ, Intens Care Unit, Affiliated Hosp, Jining, Shandong, Peoples R China

来源：

ANALYTICAL CELLULAR PATHOLOGY | 2018年 / 2018卷

关键词：

CELL-PROLIFERATION; RNA; CHEMORESISTANCE; EXPRESSION; GROWTH;

D O I：

10.1155/2018/9275685

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Medulloblastoma is the most common malignant brain tumor of childhood, with great potential to metastasize. However, the mechanisms of how medulloblastoma develops and progresses remain to be elucidated. The present study assessed the role of long noncoding RNA LOXL1-AS1 (lncRNA LOXL1-AS1) in the cell proliferation and metastasis in human medulloblastoma. It was initially found that LOXL1-AS1 was significantly overexpressed in clinical medulloblastoma tissues compared with the adjacent noncancerous tissues. LOXL1-AS1 was also highly expressed in medulloblastoma at advanced stages and differentially expressed in a series of medulloblastoma cell lines. Knockdown of LOXL1-AS1 using shRNAs significantly inhibited cell viability and colony formation capacities in D283 and D341 cells. Moreover, the cell proportion in the S phase was significantly increased, while the cell proportion in the G2/M phase was decreased after knockdown of LOXL1-AS1 in D283 cells and D341 cells. Cell cycle arrest led to eventual cell apoptosis by LOXL1-AS1 knockdown. Moreover, in a xenograft model of human medulloblastoma, knockdown of LOXL1-AS1 significantly inhibited tumor growth and promoted tumor cell apoptosis. In addition, knockdown of LOXL1-AS1 inhibited cell migration and reversed epithelial-to-mesenchymal transition (EMT). Western blot analysis further revealed that knockdown of LOXL1-AS1 decreased the phosphorylated levels of PI3K and AKT without affecting their total protein levels. These results suggest that LncRNA LOXL1-AS1 promoted the proliferation and metastasis of medulloblastoma by activating the PI3K-AKT pathway, providing evidence that knockdown of LncRNA LOXL1-AS1 might be a potential therapeutic strategy against medulloblastoma.

引用

页数：11

共 26 条

[1] Epithelial-Mesenchymal Transitions in development and disease: old views and new perspectives [J].

Angela Nieto, M. .

INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 2009, 53 (8-10) :1541-1547

[2] Small-Molecule Inhibitors of Phosphatidylinositol 3-Kinase/Akt Signaling Inhibit Wnt/β-Catenin Pathway Cross-Talk and Suppress Medulloblastoma Growth [J].

Baryawno, Ninib ;

Sveinbjornsson, Baldur ;

Eksborg, Staffan ;

Chen, Ching-Shih ;

Kogner, Per ;

Johnsen, John Inge .

CANCER RESEARCH, 2010, 70 (01) :266-276

[3] Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia [J].

Chen, Lianxiang ;

Wang, Wei ;

Cao, Lixia ;

Li, Zhijun ;

Wang, Xing .

MOLECULES AND CELLS, 2016, 39 (04) :330-336

[4] Targeting the PI3K/AKT/mTOR Signaling Pathway in Medulloblastoma [J].

Dimitrova, V. ;

Arcaro, A. .

CURRENT MOLECULAR MEDICINE, 2015, 15 (01) :82-93

[5] The PI3K inhibitor GDC-0941 displays promising in vitro and in vivo efficacy for targeted medulloblastoma therapy [J].

Ehrhardt, Michael ;

Craveiro, Rogerio B. ;

Holst, Martin I. ;

Pietsch, Torsten ;

Dilloo, Dagmar .

ONCOTARGET, 2015, 6 (02) :802-813

[6] Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial [J].

Gajjar, Amar ;

Chintagumpala, Murali ;

Ashley, David ;

Kellie, Stewart ;

Kun, Larry E. ;

Merchant, Thomas E. ;

Woo, Shaio ;

Wheeler, Greg ;

Ahern, Valerie ;

Krasin, Matthew J. ;

Fouladi, Maryam ;

Broniscer, Alberto ;

Krance, Robert ;

Hale, Gregory A. ;

Stewart, Clinton F. ;

Dauser, Robert ;

Sanford, Robert A. ;

Fuller, Christine ;

Lau, Ching ;

Boyett, James M. ;

Wallace, Dana ;

Gilbertson, Richard J. .

LANCET ONCOLOGY, 2006, 7 (10) :813-820

[7] Long noncoding RNA CCAT1 promotes cell proliferation and metastasis in human medulloblastoma via MAPK pathway [J].

Gao, Ran ;

Zhang, Rui ;

Zhang, Cuicui ;

Zhao, Li ;

Zhang, Yue .

TUMORI JOURNAL, 2018, 104 (01) :43-50

[8] Targeting the PI3K p110α Isoform Inhibits Medulloblastoma Proliferation, Chemoresistance, and Migration [J].

Guerreiro, Ana S. ;

Fattet, Sarah ;

Fischer, Barbara ;

Shalaby, Tarek ;

Jackson, Shaun P. ;

Schoenwaelder, Simone M. ;

Grotzer, Michael A. ;

Delattre, Olivier ;

Arcaro, Alexandre .

CLINICAL CANCER RESEARCH, 2008, 14 (21) :6761-6769

[9] Phosphatidylinositol 3′-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN [J].

Hartmann, Wolfgang ;

Digon-Soentgerath, Boris ;

Koch, Arend ;

Waha, Anke ;

Endl, Elmar ;

Dani, Indra ;

Denkhaus, Dorota ;

Goodyer, Cynthia G. ;

Soerensen, Niels ;

Wiestler, Otmar D. ;

Pietsch, Torsten .

CLINICAL CANCER RESEARCH, 2006, 12 (10) :3019-3027

[10] Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus [J].

Hauser, Michael A. ;

Aboobakar, Inas F. ;

Liu, Yutao ;

Miura, Shiroh ;

Whigham, Benjamin T. ;

Challa, Pratap ;

Wheeler, Joshua ;

Williams, Andrew ;

Santiago-Turla, Cecelia ;

Qin, Xuejun ;

Rautenbach, Robyn M. ;

Ziskind, Ari ;

Ramsay, Michele ;

Uebe, Steffen ;

Song, Lingyun ;

Safi, Alexias ;

Vithana, Eranga N. ;

Mizoguchi, Takanori ;

Nakano, Satoko ;

Kubota, Toshiaki ;

Hayashi, Ken ;

Manabe, Shin-ichi ;

Kazama, Shigeyasu ;

Mori, Yosai ;

Miyata, Kazunori ;

Yoshimura, Nagahisa ;

Reis, Andre ;

Crawford, Gregory E. ;

Pasutto, Francesca ;

Carmichael, Trevor R. ;

Williams, Susan E. I. ;

Ozaki, Mineo ;

Aung, Tin ;

Khor, Chiea-Chuen ;

Stamer, W. Daniel ;

Ashley-Koch, Allison E. ;

Allingham, R. Rand .

HUMAN MOLECULAR GENETICS, 2015, 24 (22) :6552-6563

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