Wang Xiaoqian, Fan Aqiang, Hong Liu
Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, China.
Transl Cancer Res. 2025 May 30;14(5):2874-2884. doi: 10.21037/tcr-24-1525. Epub 2025 May 9.
Understanding the regulatory mechanisms behind colon cancer (CC) pathogenesis is crucial for developing effective therapeutic strategies. Long non-coding RNA (lncRNA) has been implicated in various cancers, including CC, where it may play a role in tumor progression. Additionally, the transcription factor cyclic adenosine monophosphate-responsive element-binding protein 3 (CREB3) has been suggested to regulate lncRNA expression, but its role in CC remains unclear. This study investigates the CREB3- regulatory axis, focusing on how this interaction influences CC cell proliferation and its potential as a therapeutic target for cancer treatment.
To explore the CREB3- axis, bioinformatics analysis was conducted to identify the promoter and predict potential transcription factor binding sites. Expression levels of CREB3 and were analyzed using The Cancer Genome Atlas (TCGA) database, which provided a broader understanding of their correlation in human CC samples. Additionally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in SW480 CC cells to validate these findings at the cellular level. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) experiments were employed to confirm the binding of CREB3 to the promoter, providing direct evidence of their interaction. Finally, functional assays, including cell proliferation assays and knockdown experiments, were carried out to assess the impact of on CREB3-induced proliferation in CC cells.
Bioinformatics and experimental analysis revealed that CREB3 directly binds to the promoter, leading to significant upregulation of transcription in CC cells. Data from TCGA and RT-qPCR analyses showed a positive correlation between CREB3 and expression in CC tissues, supporting the hypothesis of a regulatory link. Functional assays demonstrated that overexpression of CREB3 enhanced CC cell proliferation, while silencing reversed this effect, indicating that mediates CREB3-induced proliferation. These results suggest that the CREB3- axis plays a critical role in CC progression.
This study highlights the CREB3- axis as a pivotal mechanism driving CC cell proliferation. Targeting this regulatory pathway may provide a novel therapeutic strategy for CC treatment, with the potential for developing lncRNA-based therapies aimed at inhibiting this axis to slow down tumor growth and progression.
了解结肠癌（CC）发病机制背后的调控机制对于制定有效的治疗策略至关重要。长链非编码RNA（lncRNA）已被证明与包括CC在内的多种癌症有关，它可能在肿瘤进展中发挥作用。此外，转录因子环磷酸腺苷反应元件结合蛋白3（CREB3）被认为可调节lncRNA表达，但其在CC中的作用仍不清楚。本研究调查了CREB3调控轴，重点关注这种相互作用如何影响CC细胞增殖及其作为癌症治疗靶点的潜力。
为了探索CREB3轴，进行了生物信息学分析以鉴定启动子并预测潜在的转录因子结合位点。使用癌症基因组图谱（TCGA）数据库分析了CREB3和的表达水平，从而更广泛地了解它们在人类CC样本中的相关性。此外，在SW480 CC细胞中进行了逆转录定量聚合酶链反应（RT-qPCR），以在细胞水平验证这些发现。采用荧光素酶报告基因测定和染色质免疫沉淀（ChIP）实验来证实CREB3与启动子的结合，提供它们相互作用的直接证据。最后，进行了包括细胞增殖测定和敲低实验在内的功能测定，以评估对CC细胞中CREB3诱导的增殖的影响。
生物信息学和实验分析表明，CREB3直接与启动子结合，导致CC细胞中转录显著上调。TCGA和RT-qPCR分析的数据显示CC组织中CREB3与表达呈正相关，支持了调控联系的假设。功能测定表明，CREB3的过表达增强了CC细胞增殖，而沉默则逆转了这种效应，表明介导了CREB3诱导的增殖。这些结果表明，CREB3轴在CC进展中起关键作用。
本研究强调了CREB3轴是驱动CC细胞增殖的关键机制。靶向这一调控途径可能为CC治疗提供一种新的治疗策略，具有开发基于lncRNA的疗法以抑制该轴从而减缓肿瘤生长和进展的潜力。
