Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer

Hsin Yi Chang, Shu Ping Ye, Shiow Lin Pan, Tzu Ting Kuo, Bia Chia Liu, Yi Lin Chen, Tsui Chin Huang

研究成果: 雜誌貢獻文章

11 引文 (Scopus)

摘要

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified. Methods: We performed gene-set enrichment analysis on the expression profiles of 70 CRC patients and revealed HMGA2 correlated genes that are targeted by several miRs including miR-194. To eliminate the oncogenic effects in HMGA2-driven CRC, we re-expressed miR-194 and found that miR-194 functions as a tumor suppressor by reducing cell proliferation and tumor growth in vitro and in vivo. Results: As a direct upstream inhibitory regulator of miR-194, overexpression of HMGA2 reduced miR-194 expression and biological activity, whereas re-expressing miR-194 in cells with high levels of HMGA2 impaired the effects of HMGA2, compromising cell survival, the epithelial-mesenchymal transition process, and drug resistance. Conclusion: Our findings demonstrate that novel molecular correlations can be discovered by revisiting transcriptome profiles. We uncover that miR-194 is as important as HMGA2, and both coordinately regulate the oncogenesis of CRC with inverted behaviors, revealing alternative molecular therapeutics for CRC patients with high HMGA2 expression.
原文英語
頁(從 - 到)3889-3900
頁數12
期刊Theranostics
7
發行號16
DOIs
出版狀態已發佈 - 2017

指紋

AT-Hook Motifs
Colorectal Neoplasms
Neoplasms
Epithelial-Mesenchymal Transition
MicroRNAs
Oncogenes
Transcriptome
Developed Countries
Drug Resistance
Genes
Cause of Death
Cell Survival
Carcinogenesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

引用此文

Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer. / Chang, Hsin Yi; Ye, Shu Ping; Pan, Shiow Lin; Kuo, Tzu Ting; Liu, Bia Chia; Chen, Yi Lin; Huang, Tsui Chin.

於: Theranostics, 卷 7, 編號 16, 2017, p. 3889-3900.

研究成果: 雜誌貢獻文章

Chang, Hsin Yi ; Ye, Shu Ping ; Pan, Shiow Lin ; Kuo, Tzu Ting ; Liu, Bia Chia ; Chen, Yi Lin ; Huang, Tsui Chin. / Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer. 於: Theranostics. 2017 ; 卷 7, 編號 16. 頁 3889-3900.
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abstract = "Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified. Methods: We performed gene-set enrichment analysis on the expression profiles of 70 CRC patients and revealed HMGA2 correlated genes that are targeted by several miRs including miR-194. To eliminate the oncogenic effects in HMGA2-driven CRC, we re-expressed miR-194 and found that miR-194 functions as a tumor suppressor by reducing cell proliferation and tumor growth in vitro and in vivo. Results: As a direct upstream inhibitory regulator of miR-194, overexpression of HMGA2 reduced miR-194 expression and biological activity, whereas re-expressing miR-194 in cells with high levels of HMGA2 impaired the effects of HMGA2, compromising cell survival, the epithelial-mesenchymal transition process, and drug resistance. Conclusion: Our findings demonstrate that novel molecular correlations can be discovered by revisiting transcriptome profiles. We uncover that miR-194 is as important as HMGA2, and both coordinately regulate the oncogenesis of CRC with inverted behaviors, revealing alternative molecular therapeutics for CRC patients with high HMGA2 expression.",
keywords = "Colorectal cancer, Drug resistance, Gene-set enrichment analysis, HMGA2, miR-194",
author = "Chang, {Hsin Yi} and Ye, {Shu Ping} and Pan, {Shiow Lin} and Kuo, {Tzu Ting} and Liu, {Bia Chia} and Chen, {Yi Lin} and Huang, {Tsui Chin}",
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T1 - Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer

AU - Chang, Hsin Yi

AU - Ye, Shu Ping

AU - Pan, Shiow Lin

AU - Kuo, Tzu Ting

AU - Liu, Bia Chia

AU - Chen, Yi Lin

AU - Huang, Tsui Chin

PY - 2017

Y1 - 2017

N2 - Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified. Methods: We performed gene-set enrichment analysis on the expression profiles of 70 CRC patients and revealed HMGA2 correlated genes that are targeted by several miRs including miR-194. To eliminate the oncogenic effects in HMGA2-driven CRC, we re-expressed miR-194 and found that miR-194 functions as a tumor suppressor by reducing cell proliferation and tumor growth in vitro and in vivo. Results: As a direct upstream inhibitory regulator of miR-194, overexpression of HMGA2 reduced miR-194 expression and biological activity, whereas re-expressing miR-194 in cells with high levels of HMGA2 impaired the effects of HMGA2, compromising cell survival, the epithelial-mesenchymal transition process, and drug resistance. Conclusion: Our findings demonstrate that novel molecular correlations can be discovered by revisiting transcriptome profiles. We uncover that miR-194 is as important as HMGA2, and both coordinately regulate the oncogenesis of CRC with inverted behaviors, revealing alternative molecular therapeutics for CRC patients with high HMGA2 expression.

AB - Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified. Methods: We performed gene-set enrichment analysis on the expression profiles of 70 CRC patients and revealed HMGA2 correlated genes that are targeted by several miRs including miR-194. To eliminate the oncogenic effects in HMGA2-driven CRC, we re-expressed miR-194 and found that miR-194 functions as a tumor suppressor by reducing cell proliferation and tumor growth in vitro and in vivo. Results: As a direct upstream inhibitory regulator of miR-194, overexpression of HMGA2 reduced miR-194 expression and biological activity, whereas re-expressing miR-194 in cells with high levels of HMGA2 impaired the effects of HMGA2, compromising cell survival, the epithelial-mesenchymal transition process, and drug resistance. Conclusion: Our findings demonstrate that novel molecular correlations can be discovered by revisiting transcriptome profiles. We uncover that miR-194 is as important as HMGA2, and both coordinately regulate the oncogenesis of CRC with inverted behaviors, revealing alternative molecular therapeutics for CRC patients with high HMGA2 expression.

KW - Colorectal cancer

KW - Drug resistance

KW - Gene-set enrichment analysis

KW - HMGA2

KW - miR-194

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