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Nuclear factor-κB signaling pathway is involved in phospholipase Cε-regulated proliferation in human renal cell carcinoma cells

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Abstract

Phospholipase Cε (PLCε), a downstream effector of small GTPase superfamily, has been identified to play a crucial role in tumorigenesis. Previously, our studies have showed that PLCε promotes proliferation of renal cell carcinoma (RCC) cells. However, the molecular mechanisms by which PLCε enhances the survival phenotype of RCC cells are still not fully instructed. In the present study, we first demonstrated that PLCε was highly expressed and had a close correlation with Ki67 protein expression in RCC tissue samples. Further, we found that downregulation of PLCε expression repressed growth and induced apoptosis in RCC cells. In addition, we reported a mechanism by which knockdown of PLCε gene potently suppressed the nuclear factor kappa (NF-κB) signaling pathway through action on inhibitor of κB kinase. Moreover, silencing PLCε gene decreased vascular endothelial growth factor (VEGF) expression, which was a downstream growth factor of NF-κB signaling pathway. Finally, downregulation of VEGF was severely enhanced by treatment cells with NF-κB specific inhibitor BAY11-7028 in PLCε knockdown cells. Taken together, these findings suggest that PLCε promotes RCC cell growth via NF-κB-mediated upregulation of VEGF.

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Acknowledgments

This work was supported by the National Natural Science Foundation of P. R. China (Grant No. 81072086).

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Authors and Affiliations

  1. The Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, People’s Republic of China

    Hong-fei Du, Li-ping Ou, Xue-dong Song, Yan-ru Fan, Xue Yang & Chun-Li Luo

  2. Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Bing Tan, Zhen Quan & Xiao-hou Wu

  3. Medical Laboratory of Chongqing Medical University, No.1 Yixueyuan Road, Yuan Jia Gang, Yu Zhong District, Chongqing, China

    Chun-Li Luo

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  1. Hong-fei Du
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Correspondence to Chun-Li Luo.

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Du, Hf., Ou, Lp., Song, Xd. et al. Nuclear factor-κB signaling pathway is involved in phospholipase Cε-regulated proliferation in human renal cell carcinoma cells. Mol Cell Biochem 389, 265–275 (2014). https://doi.org/10.1007/s11010-013-1948-4

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