MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma

Lu Kai Wang, Tzu Hung Hsiao, Tse-Ming Hong, Hsuan Yu Chen, Shih Han Kao, Wen Lung Wang, Sung Liang Yu, Ching Wen Lin, Pan Chyr Yang

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Non-small cell lung cancers (NSCLCs) cause high mortality worldwide, and the cancer progression can be activated by several genetic events causing receptor dysregulation, including mutation or amplification. MicroRNAs are a group of small non-coding RNA molecules that function in gene silencing and have emerged as the fine-tuning regulators during cancer progression. MiR-133a is known as a key regulator in skeletal and cardiac myogenesis, and it acts as a tumor suppressor in various cancers. This study demonstrates that miR-133a expression negatively correlates with cell invasiveness in both transformed normal bronchial epithelial cells and lung cancer cell lines. The oncogenic receptors in lung cancer cells, including insulin-like growth factor 1 receptor (IGF-1R), TGF-beta receptor type-1 (TGFBR1), and epidermal growth factor receptor (EGFR), are direct targets of miR-133a. MiR-133a can inhibit cell invasiveness and cell growth through suppressing the expressions of IGF-1R, TGFBR1 and EGFR, which then influences the downstream signaling in lung cancer cell lines. The cell invasive ability is suppressed in IGF-1R- and TGFBR1-repressed cells and this phenomenon is mediated through AKT signaling in highly invasive cell lines. In addition, by using the in vivo animal model, we find that ectopically-expressing miR-133a dramatically suppresses the metastatic ability of lung cancer cells. Accordingly, patients with NSCLCs who have higher expression levels of miR-133a have longer survival rates compared with those who have lower miR-133a expression levels. In summary, we identified the tumor suppressor role of miR-133a in lung cancer outcome prognosis, and we demonstrated that it targets several membrane receptors, which generally produce an activating signaling network during the progression of lung cancer.

Original languageEnglish
Article numbere96765
JournalPloS one
Volume9
Issue number5
DOIs
Publication statusPublished - 2014 May 9

Fingerprint

cell invasion
lung neoplasms
MicroRNAs
microRNA
Non-Small Cell Lung Carcinoma
carcinoma
lungs
Cells
Cell Membrane
Lung Neoplasms
Membranes
Transforming Growth Factor beta Receptors
receptors
Somatomedin Receptors
Transforming Growth Factor beta1
Somatomedins
transforming growth factor beta
neoplasms
cells
Epidermal Growth Factor Receptor

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wang, Lu Kai ; Hsiao, Tzu Hung ; Hong, Tse-Ming ; Chen, Hsuan Yu ; Kao, Shih Han ; Wang, Wen Lung ; Yu, Sung Liang ; Lin, Ching Wen ; Yang, Pan Chyr. / MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma. In: PloS one. 2014 ; Vol. 9, No. 5.
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abstract = "Non-small cell lung cancers (NSCLCs) cause high mortality worldwide, and the cancer progression can be activated by several genetic events causing receptor dysregulation, including mutation or amplification. MicroRNAs are a group of small non-coding RNA molecules that function in gene silencing and have emerged as the fine-tuning regulators during cancer progression. MiR-133a is known as a key regulator in skeletal and cardiac myogenesis, and it acts as a tumor suppressor in various cancers. This study demonstrates that miR-133a expression negatively correlates with cell invasiveness in both transformed normal bronchial epithelial cells and lung cancer cell lines. The oncogenic receptors in lung cancer cells, including insulin-like growth factor 1 receptor (IGF-1R), TGF-beta receptor type-1 (TGFBR1), and epidermal growth factor receptor (EGFR), are direct targets of miR-133a. MiR-133a can inhibit cell invasiveness and cell growth through suppressing the expressions of IGF-1R, TGFBR1 and EGFR, which then influences the downstream signaling in lung cancer cell lines. The cell invasive ability is suppressed in IGF-1R- and TGFBR1-repressed cells and this phenomenon is mediated through AKT signaling in highly invasive cell lines. In addition, by using the in vivo animal model, we find that ectopically-expressing miR-133a dramatically suppresses the metastatic ability of lung cancer cells. Accordingly, patients with NSCLCs who have higher expression levels of miR-133a have longer survival rates compared with those who have lower miR-133a expression levels. In summary, we identified the tumor suppressor role of miR-133a in lung cancer outcome prognosis, and we demonstrated that it targets several membrane receptors, which generally produce an activating signaling network during the progression of lung cancer.",
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MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma. / Wang, Lu Kai; Hsiao, Tzu Hung; Hong, Tse-Ming; Chen, Hsuan Yu; Kao, Shih Han; Wang, Wen Lung; Yu, Sung Liang; Lin, Ching Wen; Yang, Pan Chyr.

In: PloS one, Vol. 9, No. 5, e96765, 09.05.2014.

Research output: Contribution to journalArticle

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AU - Hsiao, Tzu Hung

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