MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1

Ching Wen Lin, Yih Leong Chang, Yu Chiuan Chang, Jau Chen Lin, Chun Chi Chen, Szu Hua Pan, Chen Tu Wu, Hsuan Yu Chen, Shuenn Chen Yang, Tse-Ming Hong, Pan Chyr Yang

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Dysregulation of microRNAs has a critical role in cancer progression. Here we identify an intronic microRNA, miR-135b that is upregulated in highly invasive non-small-cell lung cancer cells. Expression of miR-135b enhances cancer cell invasive and migratory abilities in vitro and promotes cancer metastasis in vivo, while specific inhibition of miR-135b by a miR-135b-specific molecular sponge and antagomirs suppresses cancer cell invasion, orthotopic lung tumour growth and metastasis in a mouse model. miR-135b targets multiple key components in the Hippo pathway, including LATS2, β-TrCP and NDR2, as well as LZTS1. Expression of miR-135b, LZTS1, LATS2 and nuclear TAZ predicts poor outcomes of non-small-cell lung cancer. We find that miR-135b is dually regulated by DNA demethylation and nuclear factor-kappaB signalling, implying that abnormal expression of miR-135b in cancer may result from inflammatory and epigenetic modulations. We conclude that miR-135b is an oncogenic microRNA and a potential therapeutic target for non-small-cell lung cancer.

Original languageEnglish
Article numberncomms2876
JournalNature communications
Volume4
DOIs
Publication statusPublished - 2013 Jun 12

Fingerprint

metastasis
MicroRNAs
lungs
Lung Neoplasms
cancer
Cells
Neoplasm Metastasis
Non-Small Cell Lung Carcinoma
Neoplasms
Porifera
Epigenomics
Tumors
Modulation
progressions
mice
Lung
tumors
deoxyribonucleic acid
DNA
Growth

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Lin, C. W., Chang, Y. L., Chang, Y. C., Lin, J. C., Chen, C. C., Pan, S. H., ... Yang, P. C. (2013). MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. Nature communications, 4, [ncomms2876]. https://doi.org/10.1038/ncomms2876
Lin, Ching Wen ; Chang, Yih Leong ; Chang, Yu Chiuan ; Lin, Jau Chen ; Chen, Chun Chi ; Pan, Szu Hua ; Wu, Chen Tu ; Chen, Hsuan Yu ; Yang, Shuenn Chen ; Hong, Tse-Ming ; Yang, Pan Chyr. / MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. In: Nature communications. 2013 ; Vol. 4.
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abstract = "Dysregulation of microRNAs has a critical role in cancer progression. Here we identify an intronic microRNA, miR-135b that is upregulated in highly invasive non-small-cell lung cancer cells. Expression of miR-135b enhances cancer cell invasive and migratory abilities in vitro and promotes cancer metastasis in vivo, while specific inhibition of miR-135b by a miR-135b-specific molecular sponge and antagomirs suppresses cancer cell invasion, orthotopic lung tumour growth and metastasis in a mouse model. miR-135b targets multiple key components in the Hippo pathway, including LATS2, β-TrCP and NDR2, as well as LZTS1. Expression of miR-135b, LZTS1, LATS2 and nuclear TAZ predicts poor outcomes of non-small-cell lung cancer. We find that miR-135b is dually regulated by DNA demethylation and nuclear factor-kappaB signalling, implying that abnormal expression of miR-135b in cancer may result from inflammatory and epigenetic modulations. We conclude that miR-135b is an oncogenic microRNA and a potential therapeutic target for non-small-cell lung cancer.",
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Lin, CW, Chang, YL, Chang, YC, Lin, JC, Chen, CC, Pan, SH, Wu, CT, Chen, HY, Yang, SC, Hong, T-M & Yang, PC 2013, 'MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1', Nature communications, vol. 4, ncomms2876. https://doi.org/10.1038/ncomms2876

MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1. / Lin, Ching Wen; Chang, Yih Leong; Chang, Yu Chiuan; Lin, Jau Chen; Chen, Chun Chi; Pan, Szu Hua; Wu, Chen Tu; Chen, Hsuan Yu; Yang, Shuenn Chen; Hong, Tse-Ming; Yang, Pan Chyr.

In: Nature communications, Vol. 4, ncomms2876, 12.06.2013.

Research output: Contribution to journalArticle

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AU - Pan, Szu Hua

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AU - Chen, Hsuan Yu

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AU - Hong, Tse-Ming

AU - Yang, Pan Chyr

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N2 - Dysregulation of microRNAs has a critical role in cancer progression. Here we identify an intronic microRNA, miR-135b that is upregulated in highly invasive non-small-cell lung cancer cells. Expression of miR-135b enhances cancer cell invasive and migratory abilities in vitro and promotes cancer metastasis in vivo, while specific inhibition of miR-135b by a miR-135b-specific molecular sponge and antagomirs suppresses cancer cell invasion, orthotopic lung tumour growth and metastasis in a mouse model. miR-135b targets multiple key components in the Hippo pathway, including LATS2, β-TrCP and NDR2, as well as LZTS1. Expression of miR-135b, LZTS1, LATS2 and nuclear TAZ predicts poor outcomes of non-small-cell lung cancer. We find that miR-135b is dually regulated by DNA demethylation and nuclear factor-kappaB signalling, implying that abnormal expression of miR-135b in cancer may result from inflammatory and epigenetic modulations. We conclude that miR-135b is an oncogenic microRNA and a potential therapeutic target for non-small-cell lung cancer.

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