Huang Tianxin, Ge Sijia, Huang Wei, Ma Tao, Sheng Yu, Chen Jing, Wu Shuzhen, Liu Zhaoxiu, Lu Cuihua
Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, China.
Transl Cancer Res. 2024 Aug 31;13(8):4028-4041. doi: 10.21037/tcr-23-2101. Epub 2024 Aug 19.
As a highly aggressive cancer, hepatocellular carcinoma (HCC) is often found at an advanced stage and has a poor prognosis. Therefore, in addition to the surgical treatment of HCC, the drug therapy for HCC is still under continuous exploration. The primary apolipoprotein of high-density lipoproteins (HDLs) is apolipoprotein A-I binding protein (AIBP), which has a significant impact on cholesterol metabolism, angiogenesis, and a wide range of inflammatory disorders, including cancer. The AIBP function in HCC is, however, yet unknown. This study aims to reveal the underlying mechanisms of AIBP influencing HCC proliferation and migration through mitogen-activated protein kinase (MAPK) pathways.
AIBP expression and its clinical prognostic association were investigated using The Cancer Genome Atlas (TCGA) data. The AIBP expression was studied in human HCC tissues using immunohistochemistry (IHC) and western blotting. Colony formation assays (CFAs) and cell counting kit-8 (CCK-8) were used to determine cell proliferation. Cell migration and invasion were evaluated using wound-healing and transwell assays. A xenograft tumor model was employed to investigate HCC cell proliferation in nude mice.
Tissues from HCC patients had much increased AIBP expression compared to nearby normal tissues. The prognosis for patients was bleak when AIBP expression was high. When AIBP was overexpressed in SMMC-7721 cells, the cells may become more proliferative, migrative, and invasive. In contrast, the HCC-LM3 cells' ability to proliferate, migrate, and invade was drastically decreased once AIBP was knocked down . Furthermore, research showed that AIBP overexpression may enhance cell proliferation in HCC. Finally, we discovered that AIBP could control the MAPK signaling pathway-involved genes expression, including P-MEK, MEK, c-Myc, P-ERK1/2, and ERK1/2, and that GDC-0994, a specific ERK1/2 inhibitor, could suppress the AIBP overexpression induced cell migration and proliferation abilities.
These findings demonstrated that the ERK/MAPK signaling pathway might be stimulated by AIBP in HCC tissues, leading to increased cell invasion, migration, and proliferation. It was hypothesized that AIBP might act as a useful prognostic and diagnostic marker for HCC.
作为一种侵袭性很强的癌症，肝细胞癌（HCC）常常在晚期才被发现，预后较差。因此，除了对HCC进行手术治疗外，针对HCC的药物治疗仍在不断探索中。高密度脂蛋白（HDL）的主要载脂蛋白是载脂蛋白A-I结合蛋白（AIBP），它对胆固醇代谢、血管生成以及包括癌症在内的多种炎症性疾病都有重大影响。然而，AIBP在HCC中的功能尚不清楚。本研究旨在揭示AIBP通过丝裂原活化蛋白激酶（MAPK）途径影响HCC增殖和迁移的潜在机制。
使用癌症基因组图谱（TCGA）数据研究AIBP表达及其临床预后相关性。采用免疫组织化学（IHC）和蛋白质印迹法在人HCC组织中研究AIBP表达。使用集落形成试验（CFA）和细胞计数试剂盒-8（CCK-8）来测定细胞增殖。采用伤口愈合试验和Transwell试验评估细胞迁移和侵袭能力。利用异种移植肿瘤模型研究裸鼠体内HCC细胞的增殖情况。
与邻近正常组织相比，HCC患者的组织中AIBP表达显著增加。AIBP表达高时患者的预后不佳。当AIBP在SMMC-7721细胞中过表达时，细胞的增殖、迁移和侵袭能力可能增强。相反，一旦AIBP被敲低，HCC-LM3细胞的增殖、迁移和侵袭能力会大幅下降。此外，研究表明AIBP过表达可能增强HCC中的细胞增殖。最后，我们发现AIBP可以调控与MAPK信号通路相关的基因表达，包括磷酸化MEK（P-MEK）、MEK、c-Myc、磷酸化细胞外信号调节激酶1/2（P-ERK1/2）和细胞外信号调节激酶1/2（ERK1/2），并且一种特异性ERK1/2抑制剂GDC-0994可以抑制AIBP过表达诱导的细胞迁移和增殖能力。
这些发现表明，AIBP可能在HCC组织中激活ERK/MAPK信号通路，导致细胞侵袭、迁移和增殖增加。据推测，AIBP可能是一种对HCC有用的预后和诊断标志物。
