Department of Thoracic Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Funct Integr Genomics. 2023 Sep 19;23(4):304. doi: 10.1007/s10142-023-01232-8.
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.
本研究旨在探讨髓鞘蛋白零样蛋白 1（MPZL1）对肺腺癌细胞干性特征的影响及其在肺腺癌细胞中的作用机制。采用实时定量聚合酶链反应（RT-qPCR）检测 mRNA 表达水平。CCK8 实验、划痕愈合实验和 Transwell 实验检测细胞增殖、迁移和侵袭能力。肿瘤球形成实验评估肿瘤干细胞样特性。LF3 阻断 β-catenin/转录因子 4（TCF-4）信号通路。建立裸鼠皮下移植瘤模型，记录肿瘤重量和体积。Western blot 实验检测 CD44、CD133、β-catenin、TCF-4 和 MPZL1 的表达水平。MPZL1 敲低后，MPZL1、β-catenin 和 TCF-4 的 mRNA 表达水平受到抑制，而过表达 MPZL1 后上述基因的 mRNA 表达水平增加。MPZL1 敲低抑制细胞增殖、迁移和侵袭，降低肿瘤球形成能力，下调 CD44 和 CD133 的表达水平。相反，MPZL1 过表达促进细胞增殖、迁移和侵袭，增强肿瘤球形成能力，上调 CD44 和 CD133 的表达水平。有趣的是，LF3 处理部分纠正了 MPZL1 过表达的作用。体内实验进一步证实了这一结果。综上所述，MPZL1 可能通过抑制 β-catenin/TCF-4 信号通路抑制肺腺癌细胞的增殖、迁移、侵袭和肺癌干细胞特性。
