J Cancer 2021; 12(21):6363-6371. doi:10.7150/jca.51338 This issue

Research Paper

RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway

Qingyuan Li1*, Qiuhua Lai1*, Chengcheng He1, Haonan Zhang1, Xingzhu Pan2, Haolin Li2, Qun Yan1, Yuxin Fang1, Side Liu1✉, Aimin Li1✉

1. Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
2. The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
* These authors contributed equally to this work.

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Citation:
Li Q, Lai Q, He C, Zhang H, Pan X, Li H, Yan Q, Fang Y, Liu S, Li A. RUNX1 regulates the proliferation and chemoresistance of colorectal cancer through the Hedgehog signaling pathway. J Cancer 2021; 12(21):6363-6371. doi:10.7150/jca.51338. Available from https://www.jcancer.org/v12p6363.htm

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Abstract

Graphic abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Our study demonstrated that RUNX1 promotes CRC proliferation and chemoresistance by activating the Hedgehog signaling pathway and ABCG2 expression.

Keywords: colorectal cancer, RUNX1, Hedgehog signaling pathway, proliferation, chemoresistance