Tumor Biology

, Volume 37, Issue 2, pp 2597–2602 | Cite as

Overexpression of Gremlin promotes non-small cell lung cancer progression

  • Yunhong Yin
  • Yie Yang
  • Liyun Yang
  • Yan Yang
  • Chunyu Li
  • Xiao Liu
  • Yiqing Qu
Original Article

Abstract

Lung cancer is the major cause of cancer-related death worldwide, and 80 % of them are non-small cell lung cancer (NSCLC) cases. Gremlin, a bone morphogenetic protein (BMP) antagonist, is overexpressed in various cancerous tissues; however, little is known about the roles of Gremlin in lung carcinogenesis, and it remains unclear whether Gremlin expression may associate with EGFR-TKI resistance. In this study, expression of Gremlin mRNA and protein in matched tumor and normal lung specimens are quantified by quantitative real-time PCR and western blot. The functional role of Gremlin in NSCLC cells was evaluated by interference RNA (siRNA). The effects of Silenced Gremlin on the resistant PC-9/GR cell line were investigated by proliferation and apoptosis analysis compared with control PC-9 cells. Our results found that Gremlin expression levels were higher in NSCLC tissues, and Gremlin was more highly expressed in PC-9/GR cells compared to PC-9 cells. Knocking down of Gremlin in PC-9/GR cells decreased cell proliferation and increased the expression of BMP7 protein. In addition, Gremlin silencing significantly potentiated apoptosis induced by gefitinib in PC-9/GR with Gremlin knockdown compared to PC-9 transfected with control shRNA, suggesting Gremlin contributes to gefitinib resistance in NSCLC. Gremlin might be explored as a candidate of therapeutic target for modulating EGFR-TKI sensitivity in NSCLC.

Keyword

Lung cancer NSCLC Gremlin EGFR-TKI PC-9/GR cells Proliferation Apoptosis Chemoresistance 

Notes

Acknowledgments

This work is supported by the National Natural Science Foundation of China, 81372333, and the Science and Technology Foundation of Shandong Province, 2014GSF118084.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yunhong Yin
    • 1
  • Yie Yang
    • 2
  • Liyun Yang
    • 3
  • Yan Yang
    • 1
  • Chunyu Li
    • 1
  • Xiao Liu
    • 1
  • Yiqing Qu
    • 1
  1. 1.Department of Respiratory MedicineQilu Hospital of Shandong UniversityJinanChina
  2. 2.Clinical LaboratoryQianfoshan Hospital of Shandong ProvinceJinanChina
  3. 3.Yinan Branch of Qilu Hospital of Shandong UniversityYinanChina

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