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miR-182-5p 通过抑制 FBXW7 促进肝门部胆管癌细胞的增殖和侵袭。

miR-182-5p promotes the proliferation and invasion of hilar cholangiocarcinoma cells by inhibiting FBXW7.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 50, Jinyu Avenue, Liangjiang New Area, Chongqing, 400016, China.

出版信息

J Cancer Res Clin Oncol. 2024 Oct 15;150(10):461. doi: 10.1007/s00432-024-05961-6.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression.

摘要

背景

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。

方法

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。

结果

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。

结论

miR-182-5p 通过靶向和抑制 FBXW7 表达促进 HCCA 细胞的增殖和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85a4/11473565/94fa2d2f31db/432_2024_5961_Fig1_HTML.jpg

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