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主要促进因子超家族结构域包含 12 种在肺癌中过度表达,并在肺腺癌细胞中表现出致癌作用。

Major Facilitator Superfamily Domain Containing 12 Is Overexpressed in Lung Cancer and Exhibits an Oncogenic Role in Lung Adenocarcinoma Cells.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.

出版信息

DNA Cell Biol. 2024 Jul;43(7):331-340. doi: 10.1089/dna.2023.0378. Epub 2024 Apr 30.

Abstract

Major facilitator superfamily domain containing 12 (MFSD12) regulates lysosomal cysteine import and promotes the proliferation and survival of melanoma cells. However, the expression and function of MFSD12 in other cancers, particularly in lung cancer, remain unclear. The expression of MFSD12 across various types of cancers and corresponding control tissues was examined using TIMER. MFSD12 expression in lung adenocarcinoma (LUAD) and its correlation with distinct clinicopathological features of LUAD patients were analyzed with UALCAN. The correlation between MFSD12 expression and survival of LUAD patients was assessed using the R package, survival, and the relationship between MFSD12 expression and immune infiltration status in LUAD was investigated using CIBERSORT. In addition, MFSD12 expression was knocked down in PC9 LUAD cells and their proliferation, capacity for expansion, cell cycle, apoptosis, and migration/invasion were evaluated through CCK-8 assays, colony formation assays, 7-AAD staining, Annexin V/PI staining, and Transwell assays, respectively. The stemness of these PC9 cells was determined through Western blotting, flow cytometry, and tumor sphere formation assays. MFSD12 mRNA levels were significantly elevated in multiple types of cancers, including LUAD. MFSD12 expression was also positively correlated with cancer stage, nodal metastasis, and infiltration of various immune cells in LUAD, and high MFSD12 levels predicted poor survival among LUAD patients. Knockdown of MFSD12 in PC9 cells resulted in decreased proliferation, attenuated colony formation capacity, cell cycle arrest, elevated apoptosis, impaired migration/invasion, and reduced stemness in PC9 cells. is an oncogene in LUAD.

摘要

主要促进剂超家族成员 12(MFSD12)调节溶酶体半胱氨酸摄取,并促进黑色素瘤细胞的增殖和存活。然而,MFSD12 在其他癌症中的表达和功能,特别是在肺癌中,仍然不清楚。使用 TIMER 检查了 MFSD12 在各种类型癌症和相应对照组织中的表达。使用 UALCAN 分析了肺腺癌(LUAD)中 MFSD12 的表达及其与 LUAD 患者不同临床病理特征的相关性。使用 R 包 survival 评估了 MFSD12 表达与 LUAD 患者生存的相关性,并使用 CIBERSORT 研究了 MFSD12 表达与 LUAD 中免疫浸润状态的关系。此外,在 PC9 LUAD 细胞中敲低 MFSD12,并通过 CCK-8 测定、集落形成测定、7-AAD 染色、Annexin V/PI 染色和 Transwell 测定分别评估其增殖、扩增能力、细胞周期、凋亡和迁移/侵袭。通过 Western blot、流式细胞术和肿瘤球体形成测定分别确定这些 PC9 细胞的干性。MFSD12 mRNA 水平在多种癌症中,包括 LUAD,均显著升高。MFSD12 表达与 LUAD 的癌症分期、淋巴结转移和各种免疫细胞浸润呈正相关,高水平的 MFSD12 预示着 LUAD 患者的生存不良。在 PC9 细胞中敲低 MFSD12 导致增殖减少、集落形成能力减弱、细胞周期停滞、凋亡增加、迁移/侵袭受损和 PC9 细胞干性降低。 在 LUAD 中是一种癌基因。

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