Encouraging insight into novel underlying mechanisms targeting abnormal biological pathways in colorectal cancer (CRC) are currently under investigation, edging closer and closer to clinical use. Of note, basic leucine zipper ATF-like transcription factor 3 (BATF3) has been implicated with the tumorigenicity of CRC. The current study aimed to elucidate the oncogenic BATF3-mediated S1PR1/p-STAT3/miR-155-3p/WDR82 axis in CRC. Initially, clinical samples of CRC tissues as well as CRC cell lines were collected to evaluate the expression patterns of BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82. Dual luciferase assay was employed to assess the binding affinity between miR-155-3p and WDR82. Artificial modulation of BATF3 (down- and overexpression) was conducted to measure the malignant phenotypes of CRC cells, while tumor-bearing mice were examined to determine the in vivo effects. BATF3 facilitated the proliferative, migratory, and invasive potential of CRC cells by upregulating S1PR1. Besides, the stimulatory effect of S1PR1 was realized via restored p-STAT3 expression. Furthermore, p-STAT3 was evidenced to heighten the expression of miR-155-3p and subsequently restrict the expression of its target gene WDR82. The in vivo assays provided data further substantiating the in vitro findings that inactivation of the BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82 axis suppresses CRC tumor growth. Collectively, the results of the present study emphasize the oncogenic function of BATF3 illustrated by the reinforcement the biological processes of proliferation, invasion, as well as the metastatic capacity of CRC cells through activating the S1PR1/p-STAT3/miR-155-3p/WDR82 axis.

目前正在研究针对结直肠癌 (CRC) 中异常生物通路的新的潜在机制，这令人鼓舞，越来越接近临床应用。值得注意的是，碱性亮氨酸拉链 ATF 样转录因子 3 (BATF3) 与 CRC 的致瘤性有关。目前的研究旨在阐明 CRC 中致癌的 BATF3 介导的 S1PR1/p-STAT3/miR-155-3p/WDR82 轴。最初，收集 CRC 组织和 CRC 细胞系的临床样本以评估 BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82 的表达模式。采用双荧光素酶测定来评估 miR-155-3p 和 WDR82 之间的结合亲和力。对 BATF3（下调和过表达）进行人工调节以测量 CRC 细胞的恶性表型，同时检查荷瘤小鼠以确定体内效应。BATF3 通过上调 S1PR1 促进 CRC 细胞的增殖、迁移和侵袭潜力。此外，S1PR1 的刺激作用是通过恢复 p-STAT3 表达来实现的。此外，p-STAT3 被证明可以提高 miR-155-3p 的表达，并随后限制其靶基因 WDR82 的表达。体内测定提供的数据进一步证实了 BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82 轴的失活抑制 CRC 肿瘤生长的体外发现。总的来说，本研究的结果强调了 BATF3 的致癌功能，通过加强增殖、侵袭、