Foxp1 is a tumor suppressor in colon cancer. However, circFoxp1 derived from Foxp1 is an oncogene. In this study, we aim to investigate the role of circFoxp1 in colon cancer and the regulatory mechanism between circFoxp1 and Foxp1. 78 human colon tumor tissues and the matched paracancerous tissues were collected. Quantitative polymerase chain reaction, immunohistochemistry, quantitative methylation-specific PCR, chromatin immunoprecipitation assay, CCK-8 assay, and Tumor xenograft in nude mice were performed. The expression of circFoxp1 was increased and Foxp1 was reduced in colon cancer tissues, which were associated with a poor overall survival rate of the patients with colon cancer. CircFoxp1 recruited DNMT1 to the promoter of Foxp1, leading to promotor hypermethylation, thereby inhibiting Foxp1 transcription. Interfering circFoxp1 by siRNA in SW620 cells significantly inhibited cell viability, while knockdown Foxp1 expression partially restored SW620 cell viability. In addition, knockdown of circFoxp1 significantly sensitized colon cancer cells to Capecitabine in vitro and vivo through regulating Foxp1. We discovered a novel epigenetic pathway that circFoxp1 regulated Foxp1 in colon cancer cells. CircFoxp1 may regulate DNA methylation and demethylation to coordinate colon cancer cell proliferation and participate in chemotherapy drug responses. Therefore, circFoxp1 may be a potential therapeutic target for colon cancer.

Foxp1 是结肠癌的抑癌基因。然而，源自 Foxp1 的 circFoxp1 是一种致癌基因。在本研究中，我们旨在研究 circFoxp1 在结肠癌中的作用以及 circFoxp1 和 Foxp1 之间的调控机制。收集了78份人结肠肿瘤组织和匹配的癌旁组织。在裸鼠中进行了定量聚合酶链反应、免疫组织化学、定量甲基化特异性 PCR、染色质免疫沉淀测定、CCK-8 测定和肿瘤异种移植。结肠癌组织中circFoxp1的表达增加而Foxp1的表达降低，这与结肠癌患者的总生存率较差有关。CircFoxp1 将 DNMT1 募集到 Foxp1 的启动子，导致启动子高甲基化，从而抑制 Foxp1 转录。在 SW620 细胞中通过 siRNA 干扰 circFoxp1 显着抑制细胞活力，而敲低 Foxp1 表达部分恢复了 SW620 细胞活力。此外，circFoxp1的敲低通过调节Foxp1在体外和体内显着使结肠癌细胞对卡培他滨敏感。我们发现了一种新的表观遗传途径，circFoxp1 在结肠癌细胞中调节 Foxp1。CircFoxp1 可能调节 DNA 甲基化和去甲基化以协调结肠癌细胞增殖并参与化疗药物反应。因此，circFoxp1 可能是结肠癌的潜在治疗靶点。circFoxp1的敲低通过调节Foxp1在体外和体内显着使结肠癌细胞对卡培他滨敏感。我们发现了一种新的表观遗传途径，circFoxp1 在结肠癌细胞中调节 Foxp1。CircFoxp1 可能调节 DNA 甲基化和去甲基化以协调结肠癌细胞增殖并参与化疗药物反应。因此，circFoxp1 可能是结肠癌的潜在治疗靶点。circFoxp1的敲低通过调节Foxp1在体外和体内显着使结肠癌细胞对卡培他滨敏感。我们发现了一种新的表观遗传途径，circFoxp1 在结肠癌细胞中调节 Foxp1。CircFoxp1 可能调节 DNA 甲基化和去甲基化以协调结肠癌细胞增殖并参与化疗药物反应。因此，circFoxp1 可能是结肠癌的潜在治疗靶点。