RUNX1-MUC13相互作用激活Wnt/β-catenin的信号传导对结直肠癌转移的影响
RUNX1-MUC13 Interaction Activates Wnt/β-Catenin Signaling Implications for Colorectal Cancer Metastasis
影响因子:10.00000
分区:生物学1区 Top / 生化与分子生物学2区
发表日期:2024
作者:
Xinyi Chen, Jingyao Tu, Mu Yang, Yuan Wang, Bo Liu, Hong Qiu, Xianglin Yuan
摘要
背景：结直肠癌（CRC）仍然是全球健康挑战，通常以晚期转移和预后不良为特征。在包括CRC在内的各种癌症中，与RUNT相关的转录因子1（RUNX1）在各种癌症中都起着双重作用。但是，尚未完全了解CRC中RUNX1的特定调节机制，尤其是其直接作用。目的：本研究旨在研究Runx1在CRC进展中的作用及其与粘蛋白13（MUC13）作为潜在调节靶标的作用。方法：与对照组相比，在CRC组织和细胞系中分析了RUNX1的表达。进行了体外和体内测定，以评估RUNX1过表达和敲低对细胞行为的影响。进行了芯片序列和RNA-seq分析以识别Runx1目标，重点是MUC13。结果：CRC组织和细胞中RUNX1表达显着上调，与晚期病理特征和患者预后不良相关。 Runx1过表达增强了CRC细胞的增殖，迁移，侵袭和G2/M相倒置，而其敲低的效果相反。 MUC13被鉴定为Runx1的直接转录靶标，其表达有助于Wnt/β-catenin信号通路的激活。 MUC13的破坏部分逆转了runx1引起的恶性表型。结论：RUNX1通过上调MUC13并激活Wnt/β-catenin途径来促进CRC的进展。该RUNX1-MUC13轴代表了管理CRC的潜在治疗靶点。
Abstract
Background: Colorectal cancer (CRC) remains a significant global health challenge, often characterized by late-stage metastasis and poor prognosis. The Runt-related transcription factor 1 (RUNX1) plays a dual role as both an oncogene and a tumor suppressor in various cancers, including CRC. However, the specific regulatory mechanisms of RUNX1 in CRC, particularly its direct roles, are not fully understood. Objective: This study aimed to investigate the role of RUNX1 in CRC progression and its interaction with Mucin 13 (MUC13) as a potential regulatory target. Methods: RUNX1 expression was analyzed in CRC tissues and cell lines compared to controls. In vitro and in vivo assays were conducted to assess the effects of RUNX1 overexpression and knockdown on cell behavior. ChIP-seq and RNA-seq analyses were performed to identify RUNX1 targets, with a focus on MUC13. Results: RUNX1 expression was significantly upregulated in CRC tissues and cells, correlating with advanced pathological characteristics and poor patient outcomes. RUNX1 overexpression enhanced CRC cell proliferation, migration, invasion, and G2/M phase arrest, while its knockdown had the opposite effects. MUC13 was identified as a direct transcriptional target of RUNX1, with its expression contributing to the activation of the Wnt/β-catenin signaling pathway. Disruption of MUC13 partially reversed the malignant phenotypes induced by RUNX1. Conclusion: RUNX1 promotes CRC progression by upregulating MUC13 and activating the Wnt/β-catenin pathway. This RUNX1-MUC13 axis represents a potential therapeutic target for managing CRC.