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MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.

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MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. / van der Deen, Margaretha; Taipaleenmäki, Hanna; Zhang, Ying; Teplyuk, Nadiya M; Gupta, Anurag; Cinghu, Senthilkumar; Shogren, Kristen; Maran, Avudaiappan; Yaszemski, Michael J; Ling, Ling; Cool, Simon M; Leong, David T; Dierkes, Christian; Zustin, Josef; Salto-Tellez, Manuel; Ito, Yoshiaki; Bae, Suk-Chul; Zielenska, Maria; Squire, Jeremy A; Lian, Jane B; Stein, Janet L; Zambetti, Gerard P; Jones, Stephen N; Galindo, Mario; Hesse, Eric; Stein, Gary S; van Wijnen, Andre J.

in: J BIOL CHEM, Jahrgang 288, Nr. 29, 29, 2013, S. 21307-21319.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

van der Deen, M, Taipaleenmäki, H, Zhang, Y, Teplyuk, NM, Gupta, A, Cinghu, S, Shogren, K, Maran, A, Yaszemski, MJ, Ling, L, Cool, SM, Leong, DT, Dierkes, C, Zustin, J, Salto-Tellez, M, Ito, Y, Bae, S-C, Zielenska, M, Squire, JA, Lian, JB, Stein, JL, Zambetti, GP, Jones, SN, Galindo, M, Hesse, E, Stein, GS & van Wijnen, AJ 2013, 'MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.', J BIOL CHEM, Jg. 288, Nr. 29, 29, S. 21307-21319. https://doi.org/10.1074/jbc.M112.445890

APA

van der Deen, M., Taipaleenmäki, H., Zhang, Y., Teplyuk, N. M., Gupta, A., Cinghu, S., Shogren, K., Maran, A., Yaszemski, M. J., Ling, L., Cool, S. M., Leong, D. T., Dierkes, C., Zustin, J., Salto-Tellez, M., Ito, Y., Bae, S-C., Zielenska, M., Squire, J. A., ... van Wijnen, A. J. (2013). MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J BIOL CHEM, 288(29), 21307-21319. [29]. https://doi.org/10.1074/jbc.M112.445890

Vancouver

van der Deen M, Taipaleenmäki H, Zhang Y, Teplyuk NM, Gupta A, Cinghu S et al. MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J BIOL CHEM. 2013;288(29):21307-21319. 29. https://doi.org/10.1074/jbc.M112.445890

Bibtex

@article{c8a38f4fd8d54ea1a7624619296493e7,
title = "MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.",
abstract = "Osteosarcoma (OS) is a primary bone tumor that is most prevalent during adolescence. RUNX2, which stimulates differentiation and suppresses proliferation of osteoblasts, is deregulated in OS. Here, we define pathological roles of RUNX2 in the etiology of OS and mechanisms by which RUNX2 expression is stimulated. RUNX2 is often highly expressed in human OS biopsies and cell lines. Small interference RNA-mediated depletion of RUNX2 inhibits growth of U2OS OS cells. RUNX2 levels are inversely linked to loss of p53 (which predisposes to OS) in distinct OS cell lines and osteoblasts. RUNX2 protein levels decrease upon stabilization of p53 with the MDM2 inhibitor Nutlin-3. Elevated RUNX2 protein expression is post-transcriptionally regulated and directly linked to diminished expression of several validated RUNX2 targeting microRNAs in human OS cells compared with mesenchymal progenitor cells. The p53-dependent miR-34c is the most significantly down-regulated RUNX2 targeting microRNAs in OS. Exogenous supplementation of miR-34c markedly decreases RUNX2 protein levels, whereas 3'-UTR reporter assays establish RUNX2 as a direct target of miR-34c in OS cells. Importantly, Nutlin-3-mediated stabilization of p53 increases expression of miR-34c and decreases RUNX2. Thus, a novel p53-miR-34c-RUNX2 network controls cell growth of osseous cells and is compromised in OS.",
keywords = "Animals, Bone Neoplasms, Cell Cycle, Cell Line, Tumor, Cell Proliferation, Core Binding Factor Alpha 1 Subunit, Cyclin-Dependent Kinase Inhibitor p21, DNA Damage, Down-Regulation, Gamma Rays, Gene Expression Regulation, Neoplastic, Humans, Mice, MicroRNAs, Osteosarcoma, Protein Stability, RNA, Messenger, Tumor Suppressor Protein p14ARF, Tumor Suppressor Protein p53",
author = "{van der Deen}, Margaretha and Hanna Taipaleenm{\"a}ki and Ying Zhang and Teplyuk, {Nadiya M} and Anurag Gupta and Senthilkumar Cinghu and Kristen Shogren and Avudaiappan Maran and Yaszemski, {Michael J} and Ling Ling and Cool, {Simon M} and Leong, {David T} and Christian Dierkes and Josef Zustin and Manuel Salto-Tellez and Yoshiaki Ito and Suk-Chul Bae and Maria Zielenska and Squire, {Jeremy A} and Lian, {Jane B} and Stein, {Janet L} and Zambetti, {Gerard P} and Jones, {Stephen N} and Mario Galindo and Eric Hesse and Stein, {Gary S} and {van Wijnen}, {Andre J}",
year = "2013",
doi = "10.1074/jbc.M112.445890",
language = "English",
volume = "288",
pages = "21307--21319",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "29",

}

RIS

TY - JOUR

T1 - MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma.

AU - van der Deen, Margaretha

AU - Taipaleenmäki, Hanna

AU - Zhang, Ying

AU - Teplyuk, Nadiya M

AU - Gupta, Anurag

AU - Cinghu, Senthilkumar

AU - Shogren, Kristen

AU - Maran, Avudaiappan

AU - Yaszemski, Michael J

AU - Ling, Ling

AU - Cool, Simon M

AU - Leong, David T

AU - Dierkes, Christian

AU - Zustin, Josef

AU - Salto-Tellez, Manuel

AU - Ito, Yoshiaki

AU - Bae, Suk-Chul

AU - Zielenska, Maria

AU - Squire, Jeremy A

AU - Lian, Jane B

AU - Stein, Janet L

AU - Zambetti, Gerard P

AU - Jones, Stephen N

AU - Galindo, Mario

AU - Hesse, Eric

AU - Stein, Gary S

AU - van Wijnen, Andre J

PY - 2013

Y1 - 2013

N2 - Osteosarcoma (OS) is a primary bone tumor that is most prevalent during adolescence. RUNX2, which stimulates differentiation and suppresses proliferation of osteoblasts, is deregulated in OS. Here, we define pathological roles of RUNX2 in the etiology of OS and mechanisms by which RUNX2 expression is stimulated. RUNX2 is often highly expressed in human OS biopsies and cell lines. Small interference RNA-mediated depletion of RUNX2 inhibits growth of U2OS OS cells. RUNX2 levels are inversely linked to loss of p53 (which predisposes to OS) in distinct OS cell lines and osteoblasts. RUNX2 protein levels decrease upon stabilization of p53 with the MDM2 inhibitor Nutlin-3. Elevated RUNX2 protein expression is post-transcriptionally regulated and directly linked to diminished expression of several validated RUNX2 targeting microRNAs in human OS cells compared with mesenchymal progenitor cells. The p53-dependent miR-34c is the most significantly down-regulated RUNX2 targeting microRNAs in OS. Exogenous supplementation of miR-34c markedly decreases RUNX2 protein levels, whereas 3'-UTR reporter assays establish RUNX2 as a direct target of miR-34c in OS cells. Importantly, Nutlin-3-mediated stabilization of p53 increases expression of miR-34c and decreases RUNX2. Thus, a novel p53-miR-34c-RUNX2 network controls cell growth of osseous cells and is compromised in OS.

AB - Osteosarcoma (OS) is a primary bone tumor that is most prevalent during adolescence. RUNX2, which stimulates differentiation and suppresses proliferation of osteoblasts, is deregulated in OS. Here, we define pathological roles of RUNX2 in the etiology of OS and mechanisms by which RUNX2 expression is stimulated. RUNX2 is often highly expressed in human OS biopsies and cell lines. Small interference RNA-mediated depletion of RUNX2 inhibits growth of U2OS OS cells. RUNX2 levels are inversely linked to loss of p53 (which predisposes to OS) in distinct OS cell lines and osteoblasts. RUNX2 protein levels decrease upon stabilization of p53 with the MDM2 inhibitor Nutlin-3. Elevated RUNX2 protein expression is post-transcriptionally regulated and directly linked to diminished expression of several validated RUNX2 targeting microRNAs in human OS cells compared with mesenchymal progenitor cells. The p53-dependent miR-34c is the most significantly down-regulated RUNX2 targeting microRNAs in OS. Exogenous supplementation of miR-34c markedly decreases RUNX2 protein levels, whereas 3'-UTR reporter assays establish RUNX2 as a direct target of miR-34c in OS cells. Importantly, Nutlin-3-mediated stabilization of p53 increases expression of miR-34c and decreases RUNX2. Thus, a novel p53-miR-34c-RUNX2 network controls cell growth of osseous cells and is compromised in OS.

KW - Animals

KW - Bone Neoplasms

KW - Cell Cycle

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Core Binding Factor Alpha 1 Subunit

KW - Cyclin-Dependent Kinase Inhibitor p21

KW - DNA Damage

KW - Down-Regulation

KW - Gamma Rays

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Mice

KW - MicroRNAs

KW - Osteosarcoma

KW - Protein Stability

KW - RNA, Messenger

KW - Tumor Suppressor Protein p14ARF

KW - Tumor Suppressor Protein p53

U2 - 10.1074/jbc.M112.445890

DO - 10.1074/jbc.M112.445890

M3 - SCORING: Journal article

C2 - 23720736

VL - 288

SP - 21307

EP - 21319

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 29

M1 - 29

ER -