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

Author

Listed:
  • Ching-Wen Lin

    (Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University)

  • Yih-Leong Chang

    (National Taiwan University)

  • Yu-Chiuan Chang

    (Institute of Biomedical Sciences, Academia Sinica)

  • Jau-Chen Lin

    (Fu Jen Catholic University)

  • Chun-Chi Chen

    (Institute of Biomedical Sciences, Academia Sinica)

  • Szu-Hua Pan

    (Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University)

  • Chen-Tu Wu

    (National Taiwan University)

  • Hsuan-Yu Chen

    (Institute of Statistical Science, Academia Sinica)

  • Shuenn-Chen Yang

    (Institute of Biomedical Sciences, Academia Sinica)

  • Tse-Ming Hong

    (Graduate institute of Clinical Medicine, National Cheng Kung University)

  • Pan-Chyr Yang

    (Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University
    Institute of Biomedical Sciences, Academia Sinica
    NTU Center for Genomic Medicine, College of Medicine, National Taiwan University)

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.

Suggested Citation

  • 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, 2013. "MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1," Nature Communications, Nature, vol. 4(1), pages 1-14, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2876
    DOI: 10.1038/ncomms2876
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