The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma

被引：52

作者：

Kaur, Harpreet ^{[1
,2
,3
]}

Ali, Sabeen Zulfiqar ^{[1
,2
]}

Huey, Lauren ^{[1
,2
]}

Hutt-Cabezas, Marianne ^{[1
,2
,3
]}

Taylor, Isabella ^{[3
]}

Mao, Xing-gang ^{[1
,2
]}

Weingart, Melanie ^{[1
,2
]}

Chu, Qian ^{[1
,2
]}

Rodriguez, Fausto J. ^{[1
,2
]}

Eberhart, Charles G. ^{[1
,2
]}

Raabe, Eric H. ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Div Neuropathol, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA

[3] Johns Hopkins Univ, Bloomberg Childrens Hosp, Div Pediat Oncol, Room 11379,1800 Orleans St, Baltimore, MD 21287 USA

来源：

CANCER LETTERS | 2016年 / 377卷 / 01期

关键词：

Glioma; Motility; Clonogenicity; GSC; HMGI-C; MOBILITY GROUP A2; AT-HOOK; 2; CHROMATIN-STRUCTURE; TARGETING HMGA2; CELL-MIGRATION; GASTRIC-CANCER; PROTEIN HMGA2; BRAIN-TUMOR; LET-7; GENE;

D O I：

10.1016/j.canlet.2016.04.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glioblastoma (GBM) contains a population of stem-like cells that promote tumor invasion and resistance to therapy. Identifying and targeting stem cell factors in GBM may lead to the development of more effective therapies. High Mobility Group AT-hook 2 (HMGA2) is a transcriptional modulator that mediates motility and self-renewal in normal and cancer stem cells. We identified increased expression of HMGA2 in the majority of primary human GBM tumors and cell lines compared to normal brain. Additionally, HMGA2 expression was increased in CD133+ GBM neurosphere cells compared to CD133- cells. Targeting HMGA2 with lentiviral short hairpin RNA (shRNA) led to decreased GBM stemness, invasion, and tumorigenicity. Ectopic expression of HMGA2 in GBM cell lines promoted stemness, invasion, and tumorigenicity. Our data suggests that targeting HMGA2 in GBM may be therapeutically beneficial. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

引用

页码：55 / 64

页数：10

共 73 条

[41] HMGA2 gene is a promising target for ovarian cancer silencing therapy [J].

Malek, Anastasia ;

Bakhidze, Elena ;

Noske, Aurelia ;

Sers, Christine ;

Aigner, Achim ;

Schaefer, Reinhold ;

Tchernitsa, Oleg .

INTERNATIONAL JOURNAL OF CANCER, 2008, 123 (02) :348-356

[42] LIN28A facilitates the transformation of human neural stem cells and promotes glioblastoma tumorigenesis through a pro-invasive genetic program [J].

Mao, Xing-gang ;

Huett-Cabezas, Marianne ;

Orr, Brent A. ;

Weingart, Melanie ;

Taylor, Isabella ;

Rajan, Anand K. D. ;

Odia, Yazmin ;

Kahlert, Ulf ;

Maciaczyk, Jarek ;

Nikkhah, Guido ;

Eberhart, Charles G. ;

Raabe, Eric H. .

ONCOTARGET, 2013, 4 (07) :1050-1064

[43] Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation [J].

Mayr, Christine ;

Hemann, Michael T. ;

Bartel, David P. .

SCIENCE, 2007, 315 (5818) :1576-1579

[44] HMGA2 Is a Driver of Tumor Metastasis [J].

Morishita, Asahiro ;

Zaidi, M. Raza ;

Mitoro, Akira ;

Sankarasharma, Devipriya ;

Szabolcs, Matthias ;

Okada, Yasunori ;

D'Armiento, Jeanine ;

Chada, Kiran .

CANCER RESEARCH, 2013, 73 (14) :4289-4299

[45] Probing into the Biological Processes Influenced by ESC Factor and Oncoprotein HMGA2 Using iPSCs [J].

Morshedi, Amir ;

Ren, Zhonglu ;

Li, Jinming ;

Droege, Peter .

STEM CELL REVIEWS AND REPORTS, 2013, 9 (04) :514-522

[46] Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 MicroRNA family [J].

Motoyama, Kazuo ;

Inoue, Hiroshi ;

Nakamura, Yoshito ;

Uetake, Hiroyuki ;

Sugihara, Kenichi ;

Mori, Masaki .

CLINICAL CANCER RESEARCH, 2008, 14 (08) :2334-2340

[47] A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation [J].

Narita, Masashi ;

Narita, Masako ;

Krizhanovsky, Vale ;

Nunez, Sabrina ;

Chicas, Agustin ;

Hearn, Stephen A. ;

Myers, Michael P. ;

Lowe, Scott W. .

CELL, 2006, 126 (03) :503-514

[48] HMGA2 Inhibits Apoptosis through Interaction with ATR-CHK1 Signaling Complex in Human Cancer Cells [J].

Natarajan, Suchitra ;

Hombach-Klonisch, Sabine ;

Droege, Peter ;

Klonisch, Thomas .

NEOPLASIA, 2013, 15 (03) :263-+

[49] Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing [J].

Newman, Martin A. ;

Thomson, J. Michael ;

Hammond, Scott M. .

RNA, 2008, 14 (08) :1539-1549

[50] Hmga2 Promotes Neural Stem Cell Self-Renewal in Young but Not Old Mice by Reducing p16Ink4a and p19Arf Expression [J].

Nishino, Jinsuke ;

Kim, Injune ;

Chada, Kiran ;

Morrison, Sean J. .

CELL, 2008, 135 (02) :227-239

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