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Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma

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Abstract

MicroRNAs (miRNAs) are involved in the pathogenesis of several cancers including skin squamous cell carcinoma (sSCC), and miR-134 is reported to possess tumor inhibition properties. The present study is an attempt to study the mechanistic role and antitumor property of miR-134 in sSCC. For this purpose, α-tocopherol PEG 1000 succinate (TPGS)-based PEGylated liposome was formulated and encapsulated with miR-134 (TP-miR-LP). CCK-8 assay results showed that miR-134 exhibited a concentration-dependent decrease in the cell viability of A-431 cells. Importantly, TPGS-based TP-miR-LP showed significantly (p < 0.05) lower cell viability compared with that of miR-134-loaded PEGylated liposome (miR-LP). Western blot analysis clearly indicates the specific targeting ability of miR-134 (TP-miR-LP) towards the Forkhead Box M1 (FOXM1) in the cancer cells. The apoptosis rate of the cells was significantly increased in TP-miR-LP (~ 38%) than that of miR-LP (~ 15%), respectively with significant inhibition of cell migration. Importantly, tumors treated with TP-miR-LP grew significantly slower compared with that of any other formulation group in the xenograft animal model. Present results clearly demonstrate the tumor suppressive effect of miR-134 through the downregulation of FOXM1 which subsequently blocks the downstream signaling pathways. These findings suggest the translational potential of miR-134 towards designing formulation strategies for sSCC treatment.

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Abbreviations

miRNA:

microRNA

sSCC:

skin squamous cell carcinoma

TPGS:

α-tocopherol PEG 1000 succinate

miR-LP:

miR-134-loaded PEGylated liposome

TP-miR-LP:

miR-134-loaded TPGS-based PEGylated liposome

Mut-LP:

mutant miR-134-loaded PEGylated liposome

N/P ratio:

nitrogen/phosphate ratio

MDR:

multidrug drug resistance

FOXM1:

Forkhead Box M1

EPR:

enhanced permeation and retention effect

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Funding

This study was supported by the Key Technologies R & D Program from the Department of Science and Technology of Henan Province (No: 162102310176).

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Authors and Affiliations

  1. Department of Dermatology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, 450003, Henan, China

    Chen Jing, Li Yan, Zhang Wei, Zhang Shoumin, Duan Ziyu & Li Jianguo

  2. Dermatology of Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Yin Guangwen & Zhang Jiangan

  3. Department of Dermatology, The First Affiliated Hospital of The Medical College, Shihezi University, Shihezi, Xinjiang, China

    Jia Xuesong

  4. Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Chen Hongxiang

Authors
  1. Chen Jing
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  2. Li Yan
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  3. Zhang Wei
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  4. Zhang Shoumin
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  9. Duan Ziyu
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  10. Li Jianguo
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Correspondence to Li Jianguo.

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All the animal protocols for the experiments were approved by the Institutional Committee on Animal Research in the Henan University People’s Hospital, Zhengzhou.

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The authors declare that they have no conflict of interest.

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Jing, C., Yan, L., Wei, Z. et al. Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma. Drug Deliv. and Transl. Res. 11, 1000–1008 (2021). https://doi.org/10.1007/s13346-020-00811-7

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