Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of General Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Bioengineered. 2022 May;13(5):12738-12748. doi: 10.1080/21655979.2022.2069383.
Phosphatidylinositol Transfer Protein, Membrane-Associated 3 (PITPNM3) often bind with chemokine (C-C motif) ligand 18 (CCL18) to promote tumor progression. However, the role of PITPNM3 in intrahepatic cholangiocarcinoma (ICC) is unclear. We first searched GEPIA database and detected the PITPNM3 expression using immunohistochemistry and real-time quantitative PCR. The results showed that PITPNM3 is high expression in ICC tissues and cells. Then we investigated the cell function of CLL18 and PITPNM3 through cell clone formation assay and transwell assay. The results indicated that CCL18 treatment promoted the proliferation, migration, and invasion of ICC cells. Silence of PITPNM3 reversed the effect of CCL18 on cell function. Simultaneously, we detected key protein expression of forkhead box O1 (FOXO1) and nuclear factor kappa B (NF-KB) through western blotting and found that CCL18 activated NF-KB pathway while inhibited FOXO1 pathway, the effect of which were attenuated by silence of PITPNM3. Finally, we confirmed which pathway affected the cell function using inhibitor of FOXO1 (AS1842856) and activator of NF-KB (Asatone). The results showed that AS1842856, not Asatone, relieved the inhibitory effect of si-PITPNM3 on the cell function of CCL18. In short, CCL18 treatment activated PITPNM3 to promote the proliferation, migration, and invasion of ICC via FOXO1 signaling pathway. These results provided a new insight for the diagnosis and therapy of ICC.
磷脂酰肌醇转移蛋白，膜相关 3（PITPNM3）常与趋化因子（C-C 基序）配体 18（CCL18）结合，促进肿瘤进展。然而，PITPNM3 在肝内胆管癌（ICC）中的作用尚不清楚。我们首先搜索了 GEPIA 数据库，并通过免疫组织化学和实时定量 PCR 检测了 PITPNM3 的表达。结果表明，PITPNM3 在 ICC 组织和细胞中高表达。然后，我们通过细胞克隆形成实验和 Transwell 实验研究了 CLL18 和 PITPNM3 的细胞功能。结果表明，CCL18 处理促进了 ICC 细胞的增殖、迁移和侵袭。沉默 PITPNM3 逆转了 CCL18 对细胞功能的影响。同时，我们通过 Western blot 检测了叉头框 O1（FOXO1）和核因子 kappa B（NF-KB）的关键蛋白表达，发现 CCL18 激活了 NF-KB 通路，同时抑制了 FOXO1 通路，沉默 PITPNM3 减弱了该作用。最后，我们使用 FOXO1 抑制剂（AS1842856）和 NF-KB 激活剂（Asatone）证实了哪个通路影响了细胞功能。结果表明，AS1842856 而非 Asatone 缓解了 si-PITPNM3 对 CCL18 细胞功能的抑制作用。总之，CCL18 处理通过 FOXO1 信号通路激活 PITPNM3 促进 ICC 的增殖、迁移和侵袭。这些结果为 ICC 的诊断和治疗提供了新的思路。
