Department of Second Ward Oncology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
Department of Cardiology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
Biol Direct. 2024 Sep 16;19(1):82. doi: 10.1186/s13062-024-00532-8.
Armadillo Repeat Containing X-Linked 1 (ARMCX1), a member of the ARM Repeat X-linked protein family, exerts inhibitory function in various tumors. However, its biological role in lung adenocarcinoma (LUAD) and the underlying molecular mechanisms require further exploration.
LUAD tissue microarrays and bioinformatic databases were used to evaluate the relationship between ARMCX1 and clinicopathological features. The influence of ARMCX1 on LUAD cell proliferation, migration, and invasion in vitro was determined by colony formation, CCK-8, EdU incorporation, cell cycle, wound healing, and Transwell assays. The impact of ARMCX1 on LUAD cell growth and metastasis in vivo was determined by subcutaneously transplanted tumor and pulmonary metastasis assays. Western blot, immunoprecipitation, immunofluorescence, cycloheximide, and proteasome inhibitor assays were finally conducted to explore the potential underlying molecular mechanisms.
ARMCX1 expression was downregulated in clinical LUAD samples due to which patient prognoses were poor. Functional experiments indicated that ARMCX1 overexpression inhibited the growth and metastasis of LUAD cells in vitro and in vivo. The molecular mechanism suggested that ARMCX1 recruits the E3 ubiquitin ligase FBXW7 for mediating ubiquitinated degradation of c-Myc, suppressing its nuclear accumulation, and ultimately inactivating cell cycle and epithelial-mesenchymal transition (EMT) signals.
ARMCX1 inhibits LUAD cell proliferation and metastasis by interacting with c-Myc and enhancing its ubiquitination and degradation. Consequently, it can act as a tumor suppressor in this disease. These results suggest that ARMCX1 is a potential target in the treatment of LUAD.
富含 ARM 重复序列的 X 连锁蛋白 1（ARMCX1）是 ARM 重复序列 X 连锁蛋白家族的成员，在多种肿瘤中发挥抑制作用。然而，其在肺腺癌（LUAD）中的生物学作用及其潜在的分子机制仍需进一步探索。
使用 LUAD 组织微阵列和生物信息学数据库评估 ARMCX1 与临床病理特征之间的关系。通过集落形成、CCK-8、EdU 掺入、细胞周期、划痕愈合和 Transwell 分析测定 ARMCX1 对 LUAD 细胞体外增殖、迁移和侵袭的影响。通过皮下移植瘤和肺转移实验测定 ARMCX1 对 LUAD 细胞体内生长和转移的影响。最后进行 Western blot、免疫沉淀、免疫荧光、环己酰亚胺和蛋白酶体抑制剂实验，以探讨潜在的分子机制。
由于 ARMCX1 在临床 LUAD 样本中表达下调，导致患者预后不良。功能实验表明，ARMCX1 过表达抑制 LUAD 细胞在体外和体内的生长和转移。分子机制表明，ARMCX1 招募 E3 泛素连接酶 FBXW7 介导 c-Myc 的泛素化降解，抑制其核积累，从而最终抑制细胞周期和上皮-间充质转化（EMT）信号。
ARMCX1 通过与 c-Myc 相互作用并增强其泛素化和降解来抑制 LUAD 细胞的增殖和转移。因此，它可以作为该疾病的肿瘤抑制因子。这些结果表明 ARMCX1 是 LUAD 治疗的潜在靶点。
