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SQSTM1/p62 is involved in docosahexaenoic acid–induced cellular autophagy in glioblastoma cell lines

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Abstract

Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the human brain and works as an anticancer agent to induce cell cycle arrest and apoptosis in glioblastoma multiforme (GBM) cell lines. However, little is known about the connection between DHA and autophagy in GBM cells. We found that high-dose DHA caused cellular autophagy in cultured U251 and U118 GBM cell lines, but there was no effect with a low dose. Moreover, after treatment with a high dose of DHA at 12, 24, and 48 h, the protein expression of SQSTM1/p62 decreased in DHA-treated U251 cells at 12 and 24 h, but increased at 48 h, while in DHA-treated U118 cells, the protein expression increased at all time points. Interestingly, the level of SQSTM1/p62 mRNA was elevated in both DHA-treated U251 and U118 cells at all time points, indicating that DHA activated SQSTM1/p62 transcription in both cell lines. Furthermore, downregulation of SQSTM1/p62 by siRNA attenuated DHA-induced cellular autophagy in both cell lines. This report confirms that high-dose DHA induces cellular autophagy in GBM cells, and demonstrates that SQSTM1/p62 acts as a regulator and participates in DHA-induced autophagy.

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Funding

This work was supported by grants of the National Natural Science Foundation of China (Grant No. 81801301), the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, and the “Qing Lan Project” of Jiangsu Province.

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Author notes

  1. Xuefeng Tan, Linqing Zou and Jianbing Qin contributed equally to this work.

Authors and Affiliations

  1. Department of Human Anatomy, Institute of Neurobiology, Medical School of Nantong University, No. 19 Qixiu Road, No. 3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China

    Xuefeng Tan, Linqing Zou, Jianbing Qin, Guohua Jin & Haoming Li

  2. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, No. 19 Qixiu Road, No. 3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China

    Xuefeng Tan, Linqing Zou, Jianbing Qin, Guohua Jin & Haoming Li

  3. Public Health School of Nantong University, Nantong, 226001, China

    Donglin Xia

  4. Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, China

    Youlang Zhou

  5. Clinical Medicine, Medical School of Nantong University, Nantong, 226001, China

    Zhuang Jiang

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  1. Xuefeng Tan
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Correspondence to Haoming Li.

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Tan, X., Zou, L., Qin, J. et al. SQSTM1/p62 is involved in docosahexaenoic acid–induced cellular autophagy in glioblastoma cell lines. In Vitro Cell.Dev.Biol.-Animal 55, 703–712 (2019). https://doi.org/10.1007/s11626-019-00387-8

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