Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, No. 48, Fenghao West Road, Lianhu District, 710077, Xi'an, Shaanxi, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, China.
BMC Cancer. 2023 Feb 21;23(1):176. doi: 10.1186/s12885-023-10652-5.
Hepatocellular carcinoma (HCC) is associated with a high occurrence, mortality, and poor prognosis. MLX interacting protein like (MLXIPL) is an important regulator of glucolipid metabolism and is involved in tumor progression. We aimed to clarify the role of MLXIPL in HCC and its underlying mechanisms.
The level of MLXIPL was predicted using bioinformatic analysis and verified using quantitative real-time PCR (qPCR), immunohistochemical analysis, and western blot. We assessed the effects of MLXIPL on biological behaviors using the cell counting kit-8, colony formation, and Transwell assay. Glycolysis was evaluated using the Seahorse method. The interaction between MLXIPL and mechanistic target of rapamycin kinase (mTOR) was confirmed using RNA immunoprecipitation and co-immunoprecipitation. mTOR expression was detected in HCC cells using qPCR, immunofluorescence analysis, and western blot.
The results showed that MLXIPL levels were elevated in both HCC tissues and HCC cell lines. Knockdown of MLXIPL impeded HCC cell growth, invasion, migration, and glycolysis. Moreover, MLXIPL combined with mTOR to induce phosphorylation of mTOR. Activated mTOR abrogated the effects on cellular processes induced by MLXIPL.
MLXIPL promoted the malignant progression of HCC by activating phosphorylation of mTOR, suggesting an important role of the combination of MLXIPL and mTOR in HCC.
肝细胞癌（HCC）的发病率、死亡率和预后均较差。MLX 相互作用蛋白样（MLXIPL）是糖脂代谢的重要调节因子，参与肿瘤进展。本研究旨在阐明 MLXIPL 在 HCC 中的作用及其潜在机制。
采用生物信息学分析预测 MLXIPL 水平，并通过定量实时 PCR（qPCR）、免疫组织化学分析和 Western blot 进行验证。我们通过细胞计数试剂盒-8、集落形成和 Transwell 检测评估 MLXIPL 对细胞生物学行为的影响。通过 Seahorse 法评估糖酵解。采用 RNA 免疫沉淀和免疫共沉淀验证 MLXIPL 与雷帕霉素靶蛋白激酶（mTOR）之间的相互作用。采用 qPCR、免疫荧光分析和 Western blot 检测 HCC 细胞中 mTOR 的表达。
结果表明，MLXIPL 水平在 HCC 组织和 HCC 细胞系中均升高。敲低 MLXIPL 可抑制 HCC 细胞的生长、侵袭、迁移和糖酵解。此外，MLXIPL 与 mTOR 结合诱导 mTOR 的磷酸化。激活的 mTOR 可阻断 MLXIPL 诱导的细胞过程的作用。
MLXIPL 通过激活 mTOR 的磷酸化促进 HCC 的恶性进展，表明 MLXIPL 和 mTOR 的结合在 HCC 中具有重要作用。
