hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells

  • Authors:
    • Zhipeng Li
    • Xiaohui Liu
    • Jie Ma
    • Tingting Zhang
    • Xuejuan Gao
    • Langxia Liu
  • View Affiliations

  • Published online on: August 7, 2018     https://doi.org/10.3892/ijo.2018.4517
  • Pages: 2200-2212
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Abstract

hnRNPK modulates selective quality-control autophagy bAbstract. A recent study has reported that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulated autophagy in leukemia cells. However, the underlying mechanism of this remains elusive. The present study assessed the role of hnRNPK in the autophagy of the 293 cell line and investigated the associated molecular mechanisms of this. It was revealed that hnRNPK-knockdown with siRNA or the CRISPR-Cas9 system could increase the level of autophagy, while hnRNPK-overexpression exerted the opposite effect in 293 cells under normal nutrient conditions. By contrast, hnRNPK-knockdown or -overexpression had no effect on serum starvation- or rapamycin-induced autophagy. Therefore, hnRNPK was likely involved in the late stage of autophagy rather than the early stage. Furthermore, it was observed that hnRNPK deficiency led to the decrease in α-tubulin K40 acetylation in hnRNPK single allele knockout (hnRNPK+/-) cells. In accordance with this result, it was revealed that the mRNA and protein levels of histone deacetylas 6 (HDAC6) were upregulated in hnRNPK+/- cells compared with the wild-type cells. As a consequence, autophagosome-lysosome fusion in hnRNPK+/- cells was significantly enhanced and could be effectively suppressed by treatment with the selective inhibitor of HDAC6, tubastatin A (Tub A). Furthermore, prominent co-localization of ubiquitin-positive aggregates with LC3-positive autophagosomes was observed in hnRNPK+/- cells, but not in the wild-type or hnRNPK+/- cells treated with Tub A. Taken together, these results suggested that hnRNPK may regulate basal autophagy through modulating the expression level of HDAC6 to influence the autophagosome-lysosome fusion.
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November-2018
Volume 53 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Li Z, Liu X, Ma J, Zhang T, Gao X and Liu L: hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells. Int J Oncol 53: 2200-2212, 2018
APA
Li, Z., Liu, X., Ma, J., Zhang, T., Gao, X., & Liu, L. (2018). hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells. International Journal of Oncology, 53, 2200-2212. https://doi.org/10.3892/ijo.2018.4517
MLA
Li, Z., Liu, X., Ma, J., Zhang, T., Gao, X., Liu, L."hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells". International Journal of Oncology 53.5 (2018): 2200-2212.
Chicago
Li, Z., Liu, X., Ma, J., Zhang, T., Gao, X., Liu, L."hnRNPK modulates selective quality-control autophagy by downregulating the expression of HDAC6 in 293 cells". International Journal of Oncology 53, no. 5 (2018): 2200-2212. https://doi.org/10.3892/ijo.2018.4517