miR-433 inhibits cancer stem cell-like properties and enhances 5-FU sensitivity by targeting YAP1 in colorectal cancer HCT-116 cells
DOI：10.3872/j.issn.1007-385x.2026.05.008
- VernacularTitle:miR-433通过靶向YAP1抑制结直肠癌HCT-116细胞的干细胞特性并提高其5-FU敏感性
- Author:
DONG Xinmin1
1
,
2
,
3
,
4
;
ZHENG Ti2△
1
,
2
,
3
,
4
;
LI Tiantian3
1
,
2
,
3
,
4
;
JUN Mei3
1
,
2
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3
,
4
;
ZHANG Jian4
1
,
2
,
3
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4
Author Information
1. Department of Medical Oncology, The Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China;
2. Department of Medical Affairs, The Affiliated Cancer Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China;
3. Graduate School, Inner Mongolia Medical University, Hohhot 010059, Inner Mongolia Autonomous Region, China;
4. Department of Radiation Oncology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China
- Publication Type:Journal Article
- Keywords:
结直肠癌；miR-433；YAP1；肿瘤干细胞特性；5-FU耐药
- From:
Chinese Journal of Cancer Biotherapy
2026;33(5):537-544
- CountryChina
- Language:Chinese
-
Abstract:
[摘 要] 目的：探讨miR-433对结直肠癌（CRC）细胞干细胞特性及5-氟尿嘧啶（5-FU）耐药性的影响，并阐明其潜在的分子调控机制。方法： 建立5-FU耐药的HCT-116细胞株。采用RT-qPCR和WB法检测miR-433及干细胞特性标志物（SOX2、OCT4、Nanog）的表达。通过双萤光素酶报告基因实验、免疫荧光和核质分离实验验证miR-433与靶基因YAP1的关系及YAP1对其亚细胞定位的影响。通过拯救实验确认miR-433/YAP1轴的功能。利用CCK-8法检测细胞对5-FU的敏感性。结果： 与亲代HCT-116/P细胞相比，耐药的HCT-116细胞株中miR-433表达显著下调（P < 0.05），而干细胞特性标志物（SOX2、OCT4、Nanog）表达上调（P < 0.05）。过表达miR-433能够抑制干细胞标志物的表达，并直接靶向YAP1，阻碍其核定位（P < 0.05）。恢复YAP1的表达能够部分逆转miR-433对干细胞标志物的抑制作用（P < 0.05）。功能上，上调miR-433显著增强了CRC细胞对5-FU的敏感性，而此效应同样可被YAP1的重新表达所削弱（P < 0.05）。结论： miR-433通过直接靶向YAP1通路，抑制CRC细胞的干细胞特性相关分子表型，并增强其对化疗药物的敏感性。miR-433/YAP1轴可能成为克服CRC 5-FU耐药的潜在新靶点。
- Full text:202606160904134718920260508.pdf
