Li Dapeng, Wang An, Wang Xuan, Shi Mengkun, Chen Xiaofeng, Lyu Yubao, Huang Dayu
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, People's Republic of China.
Department of Thoracic Surgery, Huashan Hospital of Fudan University, Shanghai, 200040, People's Republic of China.
Eur J Med Res. 2025 Apr 1;30(1):221. doi: 10.1186/s40001-025-02500-y.
Lung adenocarcinoma (LUAD) is a major contributor to global mortality. Grounded onto bioinformatics insights, this study probes the functions of dynein light chain LC8-type 1 (DYNLL1) in LUAD progression.
DYNLL1 levels in LUAD and normal cells were determined using qPCR and western blotting analyses. Lentiviral plasmids-mediated DYNLL1 silencing was induced in LUAD cells, followed by functional assays to investigate DYNLL1's impacts on proliferation, mobility, apoptosis, and cell cycle distribution. KY19382, a Wnt/β-catenin agonist, was employed to analyze the involvement of the Wnt/β-catenin pathway in DYNLL1's effects. Upstream regulator of DYNLL1 was queried using bioinformatics. Mouse LUAD cells LA795 were implanted into BALB/c nude mice to establish animal tumor models.
DYNLL1 exhibited heightened expression in LUAD cells. Its artificial silencing reduced proliferation and dissemination of cancer cells, promoted cell apoptosis, and induced G0/G1 cell cycle arrest. DYNLL1 silencing reduced β-catenin levels in cancer cells, and KY19382 treatment diminished the effects induced by DYNLL1 silencing. TEA domain transcription factor 4 (TEAD4), upregulated in LUAD cells, binds to the DUNLL1 promoter for transcriptional activation. TEAD4 silencing in LUAD cells reduced DYNLL1 transcription and β-catenin levels, thus suppressing proliferation while promoting apoptosis, senescence, and cell cycle arrest. In vivo, TEAD4 silencing weakened tumorigenesis of LA795 cells. Nevertheless, these phenomena were counteracted by the artificial DYNLL1 restoration in LUAD cells.
This investigation demonstrates a TEAD4-DYNLL1 axis that accelerates cell cycle progression and augments malignant properties of LUAD cells via the Wnt/β-catenin pathway.
肺腺癌（LUAD）是全球死亡率的主要促成因素。基于生物信息学见解，本研究探究动力蛋白轻链LC8型1（DYNLL1）在LUAD进展中的功能。
使用qPCR和蛋白质印迹分析确定LUAD细胞和正常细胞中DYNLL1的水平。在LUAD细胞中诱导慢病毒质粒介导的DYNLL1沉默，随后进行功能测定，以研究DYNLL1对增殖、迁移、凋亡和细胞周期分布的影响。使用Wnt/β-连环蛋白激动剂KY19382分析Wnt/β-连环蛋白途径在DYNLL1作用中的参与情况。使用生物信息学查询DYNLL1的上游调节因子。将小鼠LUAD细胞LA795植入BALB/c裸鼠中以建立动物肿瘤模型。
DYNLL1在LUAD细胞中表达升高。其人工沉默减少了癌细胞的增殖和扩散，促进了细胞凋亡，并诱导了G0/G1细胞周期停滞。DYNLL1沉默降低了癌细胞中β-连环蛋白的水平，KY19382处理减弱了DYNLL1沉默诱导的作用。在LUAD细胞中上调的TEA结构域转录因子4（TEAD4）与DUNLL1启动子结合以进行转录激活。LUAD细胞中的TEAD4沉默降低了DYNLL1转录和β-连环蛋白水平，从而抑制增殖，同时促进凋亡、衰老和细胞周期停滞。在体内，TEAD4沉默减弱了LA795细胞的肿瘤发生。然而，LUAD细胞中的人工DYNLL1恢复抵消了这些现象。
本研究证明了一个TEAD4-DYNLL1轴，该轴通过Wnt/β-连环蛋白途径加速细胞周期进程并增强LUAD细胞的恶性特性。
