Frequent overexpression of HMGA2 in human atypical teratoid/rhabdoid tumor and its correlation with let-7a3/let-7b miRNA

Keqiang Zhang, Hanlin Gao, Xiwei Wu, Jinhui Wang, Wendi Zhou, Guihua Sun, Jinghan Wang, Yafan Wang, Bing Mu, Charles Kim, Peiguo Chu, Donald M. Ho, David K. Ann, Tai Tong Wong, Yun Yen

研究成果: 雜誌貢獻文章

22 引文 (Scopus)

摘要

Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b micro- RNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT. Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1 -/- ) were investigated by antisense inhibition and ectopic overexpression studies. Results: The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = 0.34; P <0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3% (15 of 18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells. Conclusion: Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of patients with AT/RT.
原文英語
頁(從 - 到)1179-1189
頁數11
期刊Clinical Cancer Research
20
發行號5
DOIs
出版狀態已發佈 - 2014

指紋

AT-Hook Motifs
MicroRNAs
Oncogene Proteins
Immunohistochemistry
Typical Teratoid Rhabdoid Tumor
Atypical Teratoid Tumor
Rhabdoid Tumor
Polymerase Chain Reaction
Tumor Suppressor Genes
Reverse Transcription

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

引用此文

Frequent overexpression of HMGA2 in human atypical teratoid/rhabdoid tumor and its correlation with let-7a3/let-7b miRNA. / Zhang, Keqiang; Gao, Hanlin; Wu, Xiwei; Wang, Jinhui; Zhou, Wendi; Sun, Guihua; Wang, Jinghan; Wang, Yafan; Mu, Bing; Kim, Charles; Chu, Peiguo; Ho, Donald M.; Ann, David K.; Wong, Tai Tong; Yen, Yun.

於: Clinical Cancer Research, 卷 20, 編號 5, 2014, p. 1179-1189.

研究成果: 雜誌貢獻文章

Zhang, K, Gao, H, Wu, X, Wang, J, Zhou, W, Sun, G, Wang, J, Wang, Y, Mu, B, Kim, C, Chu, P, Ho, DM, Ann, DK, Wong, TT & Yen, Y 2014, 'Frequent overexpression of HMGA2 in human atypical teratoid/rhabdoid tumor and its correlation with let-7a3/let-7b miRNA', Clinical Cancer Research, 卷 20, 編號 5, 頁 1179-1189. https://doi.org/10.1158/1078-0432.CCR-13-1452
Zhang, Keqiang ; Gao, Hanlin ; Wu, Xiwei ; Wang, Jinhui ; Zhou, Wendi ; Sun, Guihua ; Wang, Jinghan ; Wang, Yafan ; Mu, Bing ; Kim, Charles ; Chu, Peiguo ; Ho, Donald M. ; Ann, David K. ; Wong, Tai Tong ; Yen, Yun. / Frequent overexpression of HMGA2 in human atypical teratoid/rhabdoid tumor and its correlation with let-7a3/let-7b miRNA. 於: Clinical Cancer Research. 2014 ; 卷 20, 編號 5. 頁 1179-1189.
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title = "Frequent overexpression of HMGA2 in human atypical teratoid/rhabdoid tumor and its correlation with let-7a3/let-7b miRNA",
abstract = "Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b micro- RNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT. Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1 -/- ) were investigated by antisense inhibition and ectopic overexpression studies. Results: The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = 0.34; P <0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3{\%} (15 of 18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells. Conclusion: Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of patients with AT/RT.",
author = "Keqiang Zhang and Hanlin Gao and Xiwei Wu and Jinhui Wang and Wendi Zhou and Guihua Sun and Jinghan Wang and Yafan Wang and Bing Mu and Charles Kim and Peiguo Chu and Ho, {Donald M.} and Ann, {David K.} and Wong, {Tai Tong} and Yun Yen",
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doi = "10.1158/1078-0432.CCR-13-1452",
language = "English",
volume = "20",
pages = "1179--1189",
journal = "Clinical Cancer Research",
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TY - JOUR

T1 - Frequent overexpression of HMGA2 in human atypical teratoid/rhabdoid tumor and its correlation with let-7a3/let-7b miRNA

AU - Zhang, Keqiang

AU - Gao, Hanlin

AU - Wu, Xiwei

AU - Wang, Jinhui

AU - Zhou, Wendi

AU - Sun, Guihua

AU - Wang, Jinghan

AU - Wang, Yafan

AU - Mu, Bing

AU - Kim, Charles

AU - Chu, Peiguo

AU - Ho, Donald M.

AU - Ann, David K.

AU - Wong, Tai Tong

AU - Yen, Yun

PY - 2014

Y1 - 2014

N2 - Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b micro- RNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT. Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1 -/- ) were investigated by antisense inhibition and ectopic overexpression studies. Results: The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = 0.34; P <0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3% (15 of 18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells. Conclusion: Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of patients with AT/RT.

AB - Purpose: Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive pediatric malignancies characterized by biallelic inactivation of the SMARCB1 tumor suppressor gene. We searched for novel genomic aberrations by investigating the copy number and expression alterations of let-7a3/let-7b micro- RNA (miRNA) and correlated these with expression of high-mobility group AT-hook 2 (HMGA2) oncoprotein, a target of let-7 miRNA family, in 18 AT/RT samples to elucidate potential roles of HMGA2 in the pathogenesis of AT/RT. Experimental Design: Genomic aberrations, let-7a3/let-7b miRNA and HMGA2 expression in AT/RT tissues were identified using quantitative PCR, reverse transcription PCR (RT-PCR), and immunohistochemistry. The impact of let-7b miRNA on HMGA2 expression and the malignant potential of human rhabdoid tumor cell G401 (SMARCB1 -/- ) were investigated by antisense inhibition and ectopic overexpression studies. Results: The copy number of let-7a3/let-7b miRNA was substantially decreased in 4 of 11 AT/RT samples. A significantly inverse correlation between let-7a3/let-7b miRNA expression and HMGA2 mRNA expression was observed in AT/RT tissues (R = 0.34; P <0.05). Immunohistochemistry analysis demonstrated that HMGA2 was highly overexpressed in 83.3% (15 of 18) of AT/RT tissues. Restoration of let-7 miRNA or knockdown of HMGA2 expression significantly suppressed proliferation and colony formation, and almost abolished the invasive potential of G401 cells. Conclusion: Reduction of let-7a3/let-7b miRNA may be one of mechanisms leading to overexpression of HMGA2 in AT/RT tissues. HMGA2 oncoprotein plays critical roles in the pathogenesis of AT/RT development; and reconstitution of let-7 miRNA or knockdown of HMGA2 oncoprotein may provide a novel therapeutic strategy for the treatment of patients with AT/RT.

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U2 - 10.1158/1078-0432.CCR-13-1452

DO - 10.1158/1078-0432.CCR-13-1452

M3 - Article

VL - 20

SP - 1179

EP - 1189

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

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