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Downregulation of pyrroline-5-carboxylate reductase-2 induces the autophagy of melanoma cells via AMPK/mTOR pathway

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Tumor Biology

Abstract

Melanoma is the most aggressive form of skin cancer and causes 50,000 deaths annually worldwide. The roles of proline-dependent process and autophagy have both been reported in studies on melanoma. In the present study, we focused on the effect of pyrroline-5-carboxylate reductase-2 (PYCR2) on inducing autophagy process in melanoma. The expression of PYCR2 was regulated by an RNAi technique, and the cell proliferation of A375 cell line was determined by methyl thiazolyl tetrazolium test; the effect of PYCR2 on the apoptosis process and AMPK/mTOR pathway was evaluated by flow cytometry assay and Western blot. It was found that silence of PYCR2 resulted in the decrease of proliferative ability and activation of AMPK/mTOR-induced autophagy of A375 cells. PYCR2 silencing also activated AMPK/mTOR pathway in another melanoma cell line, CHL-1. However, the overexpression of PYCR2 seemed to make no difference to the cell viability and targeted pathway. Our results offered a preliminary illustration on the mechanism of the PYCR2-dependent autophagy and showed that PYCR2 was a potential therapeutic target of melanoma.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81272987, 81373075, 81371748).

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    Authors and Affiliations

    1. Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China

      Rongying Ou

    2. Department of Dermatovenerology, the First Affiliated Hospital of Wenzhou Medical University; Institute of Dermatovenerology, Wenzhou Medical University, South Baixiang Road, Ouhai District, Wenzhou, 325000, China

      Xueqi Zhang, Jianfeng Cai, Xiaohong Shao, Mingfen Lv, Wei Qiu, Xuan Xuan, Jingjing Liu, Zhiming Li & Yunsheng Xu

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    Correspondence to Zhiming Li or Yunsheng Xu.

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    Rongying Ou and Xueqi Zhang contributed equally to this work.

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    Ou, R., Zhang, X., Cai, J. et al. Downregulation of pyrroline-5-carboxylate reductase-2 induces the autophagy of melanoma cells via AMPK/mTOR pathway. Tumor Biol. 37, 6485–6491 (2016). https://doi.org/10.1007/s13277-015-3927-8

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