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MPZL1 suppresses the cancer stem-like properties of lung cancer through β-catenin/TCF4 signaling

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Abstract

This study was designed to explore the influence of myelin protein zero-like protein 1 (MPZL1) on the stem-like properties of cancer cells and the underlying mechanism in lung adenocarcinoma. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to evaluate mRNA expression level. CCK8, wound healing, and transwell assays were applied to assess cell proliferation, migration, and invasion. Tumorsphere-formation assay was utilized to assess cancer stem cell–like properties. LF3 was used to block the β-catenin/Transcription factor 4 (TCF-4) signaling. Xenograft nude mouse model was conducted; tumor weight and volume were recorded. Western blot assay was utilized to detect the expression levels of CD44, CD133, β-catenin, TCF-4, and MPZL1. Following MPZL1 knockdown, the mRNA expression levels of MPZL1, β-catenin, and TCF-4 were inhibited, while the mRNA expression levels of the above genes were increased after the MPZL1 overexpression. MPZL1 knockdown suppressed cell proliferation, migration, and invasion, reduced the tumorsphere-formation capacity, and restrained the expression levels of CD44 and CD133. However, MPZL1 overexpression promoted the cell proliferation, migration, and invasion, enhanced the tumorsphere-formation capacity, and increased the expression levels of CD44 and CD133. Interestingly, LF3 treatment partially revised the effect of MPZL1 overexpression. These findings were further corroborated by in vivo experiments. We concluded that MPZL1 could suppress the lung adenocarcinoma cells’ proliferation, migration, invasion, and lung cancer stem cells characteristics. The underlying mechanism is involved in the activation of β-catenin/TCF-4 signaling.

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Data availability

The dataset used and/or analyzed in this study is available from the corresponding author on reasonable request.

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Funding

This study was supported by the Natural Science Research Project of Anhui Educational Committee (2022AH051513).

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Authors

Contributions

Conceived and designed the study: Ansheng Wang and Qiao Ge; performed the literature search and data extraction: Chao Li, Haining Hong, and Kangwu Wang; analyzed the data: Chao Zhou, Chao Zang, and Liwei Chen; Drafted the manuscript: Ansheng Wang and Haonan Zhu.

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Correspondence to Haonan Zhu or Ansheng Wang.

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The experimental procedure followed the US National Institutes of Health Guide for the Care and Use of Laboratory Animals (National Research Council, 1996). The study protocol was approved by the Animal Ethics Committee of Bengbu Medical College (approval number: 2023-436).

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The authors declare no competing interests.

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Ge, Q., Zhou, C., Zang, C. et al. MPZL1 suppresses the cancer stem-like properties of lung cancer through β-catenin/TCF4 signaling. Funct Integr Genomics 23, 304 (2023). https://doi.org/10.1007/s10142-023-01232-8

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  • DOI: https://doi.org/10.1007/s10142-023-01232-8

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