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剪接因子3b亚基4(SF3b4)由EP300和CREBBP介导,通过增强自噬促进结直肠癌(CRC)增殖。

Splicing factor 3b subunit 4 (SF3b4) is mediated by EP300 and CREBBP to promote colorectal cancer (CRC) proliferation by enhancing autophagy.

作者信息

Wu Tianhao, Xiao Zhongxiang, Su Bowen, Yan Zaihua, Zhao Yv, Huang Cheng, Zhou Lu, Tian Hongpeng, Zhang Guangjun

机构信息

Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College/Institute of Hepatobiliary Pancreatic and Intestinal Disease, North Sichuan Medical College Nanchong, Sichuan, China.

出版信息

Am J Cancer Res. 2025 Jun 25;15(6):2826-2842. doi: 10.62347/AHXI2343. eCollection 2025.

Abstract

Splicing factor 3b subunit 4 (SF3b4) is closely associated with cancer development. As a core subunit of the SF3b complex, SF3b4 participates in regulating alternative splicing, and its abnormal expression is linked to the onset of malignant tumors. However, the role of SF3b4 in colorectal cancer (CRC) remains undefined. This study demonstrates that in CRC, E1A binding protein p300 (EP300) and CREB binding protein (CREBBP) regulate SF3b4 expression by activating Histone H3 lysine 27 acetylation (H3K27ac) on the SF3b4 promoter. Additionally, enhanced autophagy counteracts the proliferation-inhibitory effect of SF3b4 knockdown in CRC cells. Implications Statement: SF3b4 may promote CRC proliferation by enhancing cellular autophagy. SF3b4 acts as a potential oncogene in CRC tumorigenesis and progression. SF3b4 serves as a promising prognostic biomarker for CRC.

摘要

剪接因子3b亚基4(SF3b4)与癌症发展密切相关。作为SF3b复合物的核心亚基,SF3b4参与调节可变剪接,其异常表达与恶性肿瘤的发生有关。然而,SF3b4在结直肠癌(CRC)中的作用仍不明确。本研究表明,在CRC中,E1A结合蛋白p300(EP300)和CREB结合蛋白(CREBBP)通过激活SF3b4启动子上的组蛋白H3赖氨酸27乙酰化(H3K27ac)来调节SF3b4的表达。此外,增强的自噬抵消了SF3b4敲低对CRC细胞增殖的抑制作用。启示声明:SF3b4可能通过增强细胞自噬促进CRC增殖。SF3b4在CRC肿瘤发生和进展中作为潜在的癌基因发挥作用。SF3b4作为CRC有前景的预后生物标志物。

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