MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol

Y. H. Yu; H. A. Chen; P. S. Chen; Y. J. Cheng; W. H. Hsu; Y. W. Chang; Y. H. Chen; Y. Jan; M. Hsiao; T. Y. Chang; Y. H. Liu; Y. M. Jeng; C. H. Wu; M. T. Huang; Y. H. Su; M. C. Hung; M. H. Chien; C. Y. Chen; M. L. Kuo; J. L. Su

doi:10.1038/onc.2012.74

MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol

Y. H. Yu, H. A. Chen, P. S. Chen, Y. J. Cheng, W. H. Hsu, Y. W. Chang, Y. H. Chen, Y. Jan, M. Hsiao, T. Y. Chang, Y. H. Liu, Y. M. Jeng, C. H. Wu, M. T. Huang, Y. H. Su, M. C. Hung, M. H. Chien, C. Y. Chen, M. L. Kuo, J. L. Su

Department of Medical Laboratory Science and Biotechnology

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129 Citations (Scopus)

Abstract

Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol - |miRNA-520h - |PP2A/C - |Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.

Original language	English
Pages (from-to)	431-443
Number of pages	13
Journal	Oncogene
Volume	32
Issue number	4
DOIs	https://doi.org/10.1038/onc.2012.74
Publication status	Published - 2013 Jan 24

All Science Journal Classification (ASJC) codes

Molecular Biology
Genetics
Cancer Research

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10.1038/onc.2012.74

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Yu, Y. H., Chen, H. A., Chen, P. S., Cheng, Y. J., Hsu, W. H., Chang, Y. W., Chen, Y. H., Jan, Y., Hsiao, M., Chang, T. Y., Liu, Y. H., Jeng, Y. M., Wu, C. H., Huang, M. T., Su, Y. H., Hung, M. C., Chien, M. H., Chen, C. Y., Kuo, M. L., & Su, J. L. (2013). MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol. Oncogene, 32(4), 431-443. https://doi.org/10.1038/onc.2012.74

@article{206d66b55dd044aa9b4942ab90ee600f,

title = "MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol",

abstract = "Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol - |miRNA-520h - |PP2A/C - |Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.",

author = "Yu, {Y. H.} and Chen, {H. A.} and Chen, {P. S.} and Cheng, {Y. J.} and Hsu, {W. H.} and Chang, {Y. W.} and Chen, {Y. H.} and Y. Jan and M. Hsiao and Chang, {T. Y.} and Liu, {Y. H.} and Jeng, {Y. M.} and Wu, {C. H.} and Huang, {M. T.} and Su, {Y. H.} and Hung, {M. C.} and Chien, {M. H.} and Chen, {C. Y.} and Kuo, {M. L.} and Su, {J. L.}",

note = "Funding Information: This work was partially supported by the National Science Council Grant (NSC-2632-B-001-MY3, NSC 96-2320-B-004-MY2, NSC 97-2320-B-039-039-MY3 and NSC 98-2815-C-039-082-B to J-LS); National Health Research Institutes Grant from Taiwan (NHRI-EX98-9712BC, NHRI-EX99-9712BC and NHRI-EX100-9712BC to J-LS); Department of Health, Executive Yuan Grant from Taiwan (DOH99-TD-G111-011 to J-LS); Grants from China Medical University (CMU96-220, CMU97-077 and CMU97-277 to J-LS; CMU-99-NTU-08, CMU100-TS-06 and DMR-101-014 to Y-HY).",

year = "2013",

month = jan,

day = "24",

doi = "10.1038/onc.2012.74",

language = "English",

volume = "32",

pages = "431--443",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "4",

}

Yu, YH, Chen, HA, Chen, PS, Cheng, YJ, Hsu, WH, Chang, YW, Chen, YH, Jan, Y, Hsiao, M, Chang, TY, Liu, YH, Jeng, YM, Wu, CH, Huang, MT, Su, YH, Hung, MC, Chien, MH, Chen, CY, Kuo, ML & Su, JL 2013, 'MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol', Oncogene, vol. 32, no. 4, pp. 431-443. https://doi.org/10.1038/onc.2012.74

TY - JOUR

T1 - MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol

AU - Yu, Y. H.

AU - Chen, H. A.

AU - Chen, P. S.

AU - Cheng, Y. J.

AU - Hsu, W. H.

AU - Chang, Y. W.

AU - Chen, Y. H.

AU - Jan, Y.

AU - Hsiao, M.

AU - Chang, T. Y.

AU - Liu, Y. H.

AU - Jeng, Y. M.

AU - Wu, C. H.

AU - Huang, M. T.

AU - Su, Y. H.

AU - Hung, M. C.

AU - Chien, M. H.

AU - Chen, C. Y.

AU - Kuo, M. L.

AU - Su, J. L.

N1 - Funding Information: This work was partially supported by the National Science Council Grant (NSC-2632-B-001-MY3, NSC 96-2320-B-004-MY2, NSC 97-2320-B-039-039-MY3 and NSC 98-2815-C-039-082-B to J-LS); National Health Research Institutes Grant from Taiwan (NHRI-EX98-9712BC, NHRI-EX99-9712BC and NHRI-EX100-9712BC to J-LS); Department of Health, Executive Yuan Grant from Taiwan (DOH99-TD-G111-011 to J-LS); Grants from China Medical University (CMU96-220, CMU97-077 and CMU97-277 to J-LS; CMU-99-NTU-08, CMU100-TS-06 and DMR-101-014 to Y-HY).

PY - 2013/1/24

Y1 - 2013/1/24

N2 - Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol - |miRNA-520h - |PP2A/C - |Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.

AB - Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol - |miRNA-520h - |PP2A/C - |Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.

UR - http://www.scopus.com/inward/record.url?scp=84873056468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873056468&partnerID=8YFLogxK

U2 - 10.1038/onc.2012.74

DO - 10.1038/onc.2012.74

M3 - Article

C2 - 22410781

AN - SCOPUS:84873056468

SN - 0950-9232

VL - 32

SP - 431

EP - 443

JO - Oncogene

JF - Oncogene

IS - 4

ER -

MiR-520h-mediated FOXC2 regulation is critical for inhibition of lung cancer progression by resveratrol

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