Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.
Department of Pharmacy, Bengbu Medical College, Bengbu, China.
Hum Gene Ther. 2023 Jun;34(11-12):540-553. doi: 10.1089/hum.2022.234.
Lung cancer (LC) is the leading cause of death worldwide, and lung adenocarcinoma (LUAD) is the most common form of LC. The abnormally high expression of myelin protein zero-like 1 (MPZL1) promotes the malignant progression of various tumors. However, there is no relevant report on the functional role of MPZL1 in LUAU. In this study, we applied Illumina sequencing to screen differentially expressed genes. Subsequently, MPZL1 was selected as hub gene for quantitative real-time polymerase chain reaction (qRT-PCR) and CCK8 assay. The expression level of MPZL1 was analyzed by immunohistochemistry, immunofluorescence, western blot, and qRT-PCR. After silencing or overexpressing MPZL1, CCK8, EDU, clone formation, scratch healing, invasion, and nude mouse tumor-bearing experiments were performed to detect the abilities of cell proliferation, migration, invasion, and tumorigenicity. Moreover, qRT-PCR, western blot, coimmunoprecipitation, and scratch healing assays were conducted to explore the transcriptional regulatory factors of MPZL1. Finally, the relationship between MPZL1 and immunotherapy was explored through public databases and validated . The results show that a total of 196 high-expressed genes and 496 low-expressed genes were screened. Differential genes are mainly enriched in cell proliferation and division, protein binding, and other pathways and functions. MPZL1 was selected as the hub gene and upregulated in LUAD tissues and cells. Silencing MPZL1 inhibited the cell proliferation and cloning formation, and the growth of tumor. Conversely, overexpression of MPZL1 has the opposite effect. In addition, MPZL1 combines with the transforming growth factor-β1 to promote the progress of LUAD. Finally, we found that high expression of MPZL1 is negatively correlated with infiltration of CD8 cells and may lead to immunotherapy resistance. In summary, this study revealed a new mechanism by which MPZL1 promotes LUAD progression by enhancing tumor proliferation, invasion, migration, and suppressing immune function.
肺癌 (LC) 是全球范围内导致死亡的主要原因，而肺腺癌 (LUAD) 是 LC 最常见的形式。髓鞘蛋白零样 1 (MPZL1) 的异常高表达促进了各种肿瘤的恶性进展。然而，目前尚无关于 MPZL1 在 LUAD 中的功能作用的相关报道。在本研究中，我们应用 Illumina 测序筛选差异表达基因。随后，选择 MPZL1 作为定量实时聚合酶链反应 (qRT-PCR) 和 CCK8 测定的枢纽基因。通过免疫组织化学、免疫荧光、western blot 和 qRT-PCR 分析 MPZL1 的表达水平。沉默或过表达 MPZL1 后，进行 CCK8、EDU、克隆形成、划痕愈合、侵袭和裸鼠荷瘤实验，以检测细胞增殖、迁移、侵袭和致瘤能力。此外，进行 qRT-PCR、western blot、共免疫沉淀和划痕愈合实验，以探索 MPZL1 的转录调节因子。最后，通过公共数据库和验证探索 MPZL1 与免疫治疗的关系。结果表明，筛选出了 196 个高表达基因和 496 个低表达基因。差异基因主要富集在细胞增殖和分裂、蛋白质结合等途径和功能中。选择 MPZL1 作为枢纽基因，并在 LUAD 组织和细胞中上调。沉默 MPZL1 抑制了细胞增殖和克隆形成以及肿瘤的生长。相反，过表达 MPZL1 则有相反的效果。此外，MPZL1 与转化生长因子-β1 结合，促进 LUAD 的进展。最后，我们发现 MPZL1 的高表达与 CD8 细胞的浸润呈负相关，可能导致免疫治疗抵抗。综上所述，本研究揭示了 MPZL1 通过增强肿瘤增殖、侵袭、迁移和抑制免疫功能促进 LUAD 进展的新机制。
