Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 50, Jinyu Avenue, Liangjiang New Area, Chongqing, 400016, China.
J Cancer Res Clin Oncol. 2024 Oct 15;150(10):461. doi: 10.1007/s00432-024-05961-6.
Hilar cholangiocarcinoma (HCCA) is a common type of cholangiocarcinoma (CHOL) that originates from the right and/or left hepatic duct near the biliary tract confluence. The objective of this study is to investigate the impact of miR-182-5p on the proliferation and invasion of HCCA cells and identify a potential target for HCCA treatment.
HCCA tissues were collected and HCCA cells were cultured. miR-182-5p and F-box and WD repeat domain containing 7 (FBXW7) were detected. After transfection of miR-182-5p inhibitor into HCCA cells, cell proliferation and invasion were detected by cell counting 8-kit and Transwell assay. FBXW7 expression was detected by Western blot. The targeted relationship between miR-182-5p and FBXW7 3'UTR was verified by dual-luciferase report assay. si-FBXW7 and miR-182-5p inhibitor were transfected into cells for combined experiments. HCCA cells with lowly-expressed miR-182-5p were injected into nude mice to establish the xenograft tumor model, and subsequent observations were made on tumor growth and gene expression changes.
miR-182-5p exhibited high expression levels in both HCCA tissues and cell lines. Inhibiting miR-182-5p effectively suppressed the proliferation and migration of HCCA cells. miR-182-5p bounded to FBXW7 3 'UTR and inhibited FBWX7 expression. Suppressing FBXW7 expression partially reversed the inhibitory effect of miR-182-5p inhibitor on HCCA cell proliferation and invasion. Silencing miR-182-5p could inhibit the HCCA growth in vivo.
miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression.
肝门部胆管癌(HCCA)是一种常见的胆管癌(CHOL)类型,起源于胆管汇合处附近的右/左肝管。本研究旨在探讨 miR-182-5p 对 HCCA 细胞增殖和侵袭的影响,并寻找 HCCA 治疗的潜在靶点。
收集 HCCA 组织并培养 HCCA 细胞。检测 miR-182-5p 和 F-box 和 WD 重复域包含 7(FBXW7)。转染 miR-182-5p 抑制剂入 HCCA 细胞后,通过细胞计数 8 试剂盒和 Transwell 测定法检测细胞增殖和侵袭。通过 Western blot 检测 FBXW7 表达。通过双荧光素酶报告试验验证 miR-182-5p 与 FBXW7 3'UTR 的靶向关系。将 si-FBXW7 和 miR-182-5p 抑制剂转染入细胞进行联合实验。将低表达 miR-182-5p 的 HCCA 细胞注入裸鼠体内建立异种移植肿瘤模型,并观察肿瘤生长和基因表达变化。
miR-182-5p 在 HCCA 组织和细胞系中均呈高表达。抑制 miR-182-5p 可有效抑制 HCCA 细胞的增殖和迁移。miR-182-5p 结合到 FBXW7 3'UTR 并抑制 FBXW7 表达。抑制 FBXW7 表达部分逆转了 miR-182-5p 抑制剂对 HCCA 细胞增殖和侵袭的抑制作用。沉默 miR-182-5p 可抑制体内 HCCA 的生长。
miR-182-5p 通过靶向和抑制 FBXW7 表达促进 HCCA 细胞的增殖和侵袭。