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MiR-342-3p inhibits LCSC oncogenicity and cell stemness through HDAC7/PTEN axis

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Abstract

Objective

This study aims to explore the effects of miR-342-3p on liver cancer stem cells (LCSC) and related mechanism.

Methods

LCSC were sorted using immunomagnetic beads and flow cytometry was used to determine CD133+ and CD133− sorted cells. The self-renewal ability and growth ability of LCSC were measured by tumor spheroid formation assay and soft agar colony formation assay. Protein and mRNA expressions of CD44, ALDH1, Bmi1, Sox2 and Oct4 were detected by western blot and quantitative PCR. The relationship between miR-342-3p and HDAC7 was analyzed by dual-luciferase assay. The acetylation level of H3 protein was measured by acetyl Lysine antibody.

Results

miR-342-3p overexpression in LCSC lead to lower tumor volume, reduced tumor spheroid formation and agar colony formation rates, as well as lower mRNA and protein expressions of CD44, ALDH1, Bmi1, Sox2, and Oct4. Dual-luciferase reporter assay confirmed HDAC7 as a target gene of miR-342-3p. Inhibition of HDAC7 or overexpression of PTEN suppressed the carcinogenicity and stemness of LCSC. PTEN expression was increased in sh-HDAC7 group and decreased in pcDNA3.1-HDAC7 group. HDAC7 promoted H3 deacetylation and inhibited PTEN expression. Overexpression of HDAC7 or silencing of PTEN could reverse the inhibitory effect of overexpression of miR-342-3p on LCSC carcinogenicity and cell stemness.

Conclusion

MiR-342-3p inhibited LCSC oncogenicity and cell stemness by promoting PTEN and inhibiting HDAC7.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

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Author notes

  1. Chunlin Xu and Weiwei Sun contributed equally to this research.

Authors and Affiliations

  1. Department of Infectious Disease (No. 3), Second Affiliated Hospital of Harbin Medical University, Harbin, 150040, Heilongjiang, People’s Republic of China

    Chunlin Xu

  2. Department of Respiratory Oncology, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150040, Heilongjiang, People’s Republic of China

    Weiwei Sun, Jinglei Liu, Haihong Pu & Yinghong Li

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  1. Chunlin Xu
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  2. Weiwei Sun
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  3. Jinglei Liu
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Correspondence to Yinghong Li.

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Xu, C., Sun, W., Liu, J. et al. MiR-342-3p inhibits LCSC oncogenicity and cell stemness through HDAC7/PTEN axis. Inflamm. Res. 71, 107–117 (2022). https://doi.org/10.1007/s00011-021-01521-7

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  • DOI: https://doi.org/10.1007/s00011-021-01521-7

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