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RASSF4 is downregulated in nonsmall cell lung cancer and inhibits cancer cell proliferation and invasion

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Tumor Biology

Abstract

RASSF4 has been implicated as a tumor suppressor in several human cancers. Its clinical significance and biological characteristics in human nonsmall cell lung cancer (NSCLC) have not been explored yet. In this study, we explored expression pattern of RASSF4 in 89 NSCLC specimens. The results showed that RASSF4 was downregulated in 36/89 NSCLC tissues compared with normal tissue. RASSF4 downregulation significantly associated with advanced TNM stage, positive nodal status, and poor prognosis. We examined RASSF4 protein expression in normal lung epithelial cell line and lung cancer lines. We found that RASSF4 expression was downregulated in four of seven lung cancer cell lines compared with normal bronchial epithelial cells. RASSF4 plasmid transfection was performed in H460 and A549 cell lines. RASSF4 overexpression inhibited proliferation, colony formation, and invading ability. In addition, we identified that RASSF4 could inhibit cell cycle progression with downregulation of cyclin D1. Expression of invasion-related protein MMP2, MMP9 was also decreased. In conclusion, the present study suggested that RASSF4 serves as an important tumor suppressor in NSCLC.

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Acknowledgments

The study was supported by the National Natural Science Foundation of China (No. 81302022).

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Authors and Affiliations

  1. Department of Pathology, First Affiliated Hospital and College of Basic Medical Science, China Medical University, Shenyang, 110001, China

    Yong Han, Qianze Dong, Jie Hao, Lin Fu, Xu Han, Xiaoying Zheng & Enhua Wang

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  1. Yong Han
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  2. Qianze Dong
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  3. Jie Hao
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  4. Lin Fu
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  5. Xu Han
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  6. Xiaoying Zheng
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  7. Enhua Wang
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Correspondence to Enhua Wang.

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Supplementary Figure 1

RASSF4 depletion upregulates H157 cell proliferation and invasion A. MTT assay in H157 cells transfected with RASSF4 siRNA. Time dependent increase in cell proliferation after RASSF4 depletion compared with control. B. Matrigel invasion assay showed that RASSF4 depletion increased cell invasion in H157 cell line. * p < 0.05. (GIF 29 kb)

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Han, Y., Dong, Q., Hao, J. et al. RASSF4 is downregulated in nonsmall cell lung cancer and inhibits cancer cell proliferation and invasion. Tumor Biol. 37, 4865–4871 (2016). https://doi.org/10.1007/s13277-015-4343-9

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  • DOI: https://doi.org/10.1007/s13277-015-4343-9

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