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

研究成果: Article

173 引文 (Scopus)

摘要

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.

原文English
文章編號ncomms2876
期刊Nature communications
4
DOIs
出版狀態Published - 2013 六月 12

指紋

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)

引用此文

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. 於: Nature communications. 2013 ; 卷 4.
@article{23e4df20755146039dd47ebafa5312dd,
title = "MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1",
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.",
author = "Lin, {Ching Wen} and Chang, {Yih Leong} and Chang, {Yu Chiuan} and Lin, {Jau Chen} and Chen, {Chun Chi} and Pan, {Szu Hua} and Wu, {Chen Tu} and Chen, {Hsuan Yu} and Yang, {Shuenn Chen} and Tse-Ming Hong and Yang, {Pan Chyr}",
year = "2013",
month = "6",
day = "12",
doi = "10.1038/ncomms2876",
language = "English",
volume = "4",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

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, 卷 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.

於: Nature communications, 卷 4, ncomms2876, 12.06.2013.

研究成果: Article

TY - JOUR

T1 - MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1

AU - Lin, Ching Wen

AU - Chang, Yih Leong

AU - Chang, Yu Chiuan

AU - Lin, Jau Chen

AU - Chen, Chun Chi

AU - Pan, Szu Hua

AU - Wu, Chen Tu

AU - Chen, Hsuan Yu

AU - Yang, Shuenn Chen

AU - Hong, Tse-Ming

AU - Yang, Pan Chyr

PY - 2013/6/12

Y1 - 2013/6/12

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878703345&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878703345&partnerID=8YFLogxK

U2 - 10.1038/ncomms2876

DO - 10.1038/ncomms2876

M3 - Article

C2 - 23695671

AN - SCOPUS:84878703345

VL - 4

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - ncomms2876

ER -