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TAT-Beclin 1 represses the carcinogenesis of DUSP4-positive PTC by enhancing autophagy

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Abstract

Background

DUSP4 is a pro-tumorigenic molecule of papillary thyroid carcinoma (PTC). DUSP4 also exists as an autophagic regulator. Moreover, DUSP4, as a negative regulator of MAPK, can prevent Beclin 1 from participating in autophagic response. This study aimed to explore whether TAT-Beclin 1, a recombinant protein of Beclin 1, could inhibit the tumorigenesis of DUSP4-positive PTC by regulating autophagy.

Methods

First, we divided PTC tissues into three groups according to DUSP4 expression levels by immunohistochemical analyses, and evaluated the relationship between autophagic molecules (Beclin 1 and LC3II) and DUSP4 using Western blotting assays. After overexpression of DUSP4 by lentiviral transduction, the in vitro and in vivo roles of TAT-Beclin 1 on DUSP4-overexpressed PTC cells were assessed (including autophagic activity, cell survival and function, and tumor growth). The roles of TAT-Beclin 1 in the survival of DUSP4-silenced PTC cells were also evaluated.

Results

Our results showed that the expression levels of autophagic proteins decreased with the increase of DUSP4 expression in PTC tissues. In PTC cells, DUSP4 overexpression-inhibited autophagic activity (including Beclin 1 expression, LC3 conversion rate and LC3-puncta formation) and -promoted cell proliferation and migration were reversed by TAT-Beclin 1 administration. In vivo assays also showed that DUSP4-overexpressed PTC cells had stronger tumorigenic ability and weaker autophagic activity, which was blocked by TAT-Beclin 1 administration.

Conclusion

TAT-Beclin 1, as an autophagic promoter, could repress the carcinogenesis of DUSP4-positive PTC, which implies that the use of TAT-Beclin 1 for the PTC patients' treatment might be determined according to the DUSP4 level in their tumors.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by The Natural Science Foundation of Hebei Province (Grant No. H2018206180).

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Authors and Affiliations

  1. Department 5 of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050005, Hebei, China

    Leilei Zang

  2. Department of Infection Management/Public Health, Hebei People’s Hospital, Shijiazhuang, 050057, Hebei, China

    Yanmei Song

  3. Department 2 of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, 050005, Hebei, China

    Yanhua Tian

  4. Department 4 of General Surgery, The Second Hospital of Hebei Medical University, No.215 Heping West Road, Xinhua District, Shijiazhuang, 050005, Hebei, China

    Ning Hu

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  1. Leilei Zang
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Contributions

NH and LLZ were responsible for conception and writing of the manuscript. LLZ, YMS and YHT performed the experimental work. All authors contributed to substantial discussion of content, reviewing and revising the manuscript before submission.

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Correspondence to Ning Hu.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Zang, L., Song, Y., Tian, Y. et al. TAT-Beclin 1 represses the carcinogenesis of DUSP4-positive PTC by enhancing autophagy. Mol Biol Rep 50, 1425–1436 (2023). https://doi.org/10.1007/s11033-022-08109-2

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  • DOI: https://doi.org/10.1007/s11033-022-08109-2

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