Li Qingyuan, Lai Qiuhua, He Chengcheng, Zhang Haonan, Pan Xingzhu, Li Haolin, Yan Qun, Fang Yuxin, Liu Side, Li Aimin
Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
J Cancer. 2021 Sep 3;12(21):6363-6371. doi: 10.7150/jca.51338. eCollection 2021.
Chemoresistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to a poor prognosis. To characterize RUNX1 expression in colorectal cancer (CRC) and elucidate its mechanistic involvement in the tumor biology of this disease. The expression of RUNX1 in CRC and normal tissues was detected by bioinformatics analysis. Cell proliferation was measured by CCK-8 and clonogenic assays. In vivo tumor progression was assessed with a xenograft mouse model. Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. RUNX1, key molecules of the Hedgehog signaling pathway, and ABCG2 were detected by qRT-PCR and Western blotting. RUNX1 expression is upregulated in CRC tissues. RUNX1 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted proliferation, and inhibited 5-FU-induced apoptosis. Mechanistically, RUNX1 can activate the Hedgehog signaling pathway and promote the expression of ABCG2 in CRC cells. Our study demonstrated that RUNX1 promotes CRC proliferation and chemoresistance by activating the Hedgehog signaling pathway and ABCG2 expression.
化疗耐药是结直肠癌(CRC)患者复发的主要原因之一,且会导致预后不良。为了表征RUNX1在结直肠癌(CRC)中的表达,并阐明其在该疾病肿瘤生物学中的机制性作用。通过生物信息学分析检测RUNX1在CRC和正常组织中的表达。通过CCK-8和克隆形成试验测量细胞增殖。用异种移植小鼠模型评估体内肿瘤进展。进行细胞药物敏感性试验和流式细胞术以分析CRC细胞的化疗耐药性。通过qRT-PCR和蛋白质印迹法检测RUNX1、Hedgehog信号通路的关键分子以及ABCG2。RUNX1在CRC组织中的表达上调。RUNX1增强了CRC细胞对5-氟尿嘧啶(5-FU)的耐药性,促进了细胞增殖,并抑制了5-FU诱导的细胞凋亡。从机制上讲,RUNX1可以激活Hedgehog信号通路并促进CRC细胞中ABCG2的表达。我们的研究表明,RUNX1通过激活Hedgehog信号通路和ABCG2表达来促进CRC增殖和化疗耐药。