Department of General Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, 570311 Haikou, Hainan, China.
Front Biosci (Landmark Ed). 2024 Nov 21;29(11):395. doi: 10.31083/j.fbl2911395.
Emerging evidence indicates the essential role of cancer stem cells (CSCs) in the development and progression of various cancers, including colorectal cancer (CRC). CELF6, a member of the cytosine-uridine-guanine-binding protein (CUG-BP), Elav-like family (CELF), has been reported to be downregulated in CRC tissues. This study aims to elucidate the role and underlying mechanisms of CELF6 in CRC progression.
The expression levels and prognostic significance of CELF6, along with its association with homeobox A5 (HOXA5), were analyzed using University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), PrognoScan, and Tumor Immune Estimation Resource (TIMER) databases. The expression of CELF6 was further assessed through quantitative real-time polymerase chain reaction (qRT-PCR), immunoblotting, and immunohistochemistry. Both and experiments were conducted to investigate the effects of CELF6 on CRC cell proliferation, stemness and tumorigenesis, and to elucidate the molecular mechanisms.
CELF6 was found to be downregulated in CRC and was associated with poor prognosis. Functional studies revealed that overexpression of CELF6 resulted in decreased CRC cell proliferation and stemness , reduced tumor growth , and induced G1 phase cell cycle arrest. Mechanistically, CELF6 regulated the expression of HOXA5 by modulating its mRNA stability. Furthermore, the knockdown of HOXA5 reversed the inhibitory effects of CELF6 on CRC cell proliferation and stemness, demonstrating that silencing HOXA5 counteracted the suppressive effects of CELF6.
This study is the first to identify CELF6 as a suppressor of stemness and a modulator of CRC progression. These findings provide new insights into the role of CELF6 in CRC and highlight its potential as a novel therapeutic target.
新兴证据表明，癌症干细胞（CSC）在各种癌症的发展和进展中起着重要作用，包括结直肠癌（CRC）。CELF6 是胞嘧啶-尿嘧啶-鸟嘌呤结合蛋白（CUG-BP）、Elav 样家族（CELF）的成员，据报道在 CRC 组织中下调。本研究旨在阐明 CELF6 在 CRC 进展中的作用和潜在机制。
使用阿拉巴马大学伯明翰分校癌症数据分析门户（UALCAN）、PrognoScan 和肿瘤免疫估计资源（TIMER）数据库分析 CELF6 的表达水平和预后意义，以及与同源盒 A5（HOXA5）的关联。通过定量实时聚合酶链反应（qRT-PCR）、免疫印迹和免疫组织化学进一步评估 CELF6 的表达。进行了和实验，以研究 CELF6 对 CRC 细胞增殖、干性和肿瘤发生的影响，并阐明分子机制。
发现 CELF6 在 CRC 中下调，与预后不良相关。功能研究表明，CELF6 的过表达导致 CRC 细胞增殖和干性降低，肿瘤生长减少，并诱导 G1 期细胞周期停滞。机制上，CELF6 通过调节其 mRNA 稳定性来调节 HOXA5 的表达。此外，HOXA5 的敲低逆转了 CELF6 对 CRC 细胞增殖和干性的抑制作用，表明沉默 HOXA5 抵消了 CELF6 的抑制作用。
这项研究首次将 CELF6 鉴定为干性的抑制剂和 CRC 进展的调节剂。这些发现为 CELF6 在 CRC 中的作用提供了新的见解，并强调了其作为一种新型治疗靶点的潜力。
