Huang Jinxi, Yuan Weiwei, Li Gaofeng, Chen Beibei, Wang Lihong, Chen Yulong, Huang Hai
Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No.127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China.
Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No.127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China.
Discov Oncol. 2025 Jun 18;16(1):1143. doi: 10.1007/s12672-025-02994-2.
With advancements in the study of long non-coding RNAs (lncRNAs) as significant biomarkers and therapeutic targets in various human diseases, including cancer, neurodegenerative conditions, and genetic disorders, emerging evidence highlights their regulatory roles in the development of gastric cancer (GC). However, the mechanisms underlying these functions remain largely unknown. In this study, we investigate the role of the LINC01048 in tumorigenesis and cell proliferation in GC cell lines, such as HGC27 and MKN45. Analysis of publicly available databases and experimental validation revealed that LINC01048 expression is elevated in GC tissues and cell lines and is associated with poor prognosis. Knockdown of LINC01048 significantly suppressed cell proliferation and induced apoptosis in GC cells. Additionally, depletion of LINC01048 reduced the nuclear localization of β-catenin while increasing its cytoplasmic retention. Furthermore, treatment with SKL2001, a Wnt/β-catenin pathway activator, reversed the effects of LINC01048 knockdown on cell proliferation and apoptosis. In vivo experiments confirmed that LINC01048 depletion decreased tumor growth in GC xenograft models. Overall, these findings suggest that LINC01048 plays an oncogenic role in GC by promoting cell proliferation and modulating the Wnt/β-catenin pathway. Therefore, LINC01048 may serve as a potential therapeutic target for GC treatment.
随着长链非编码RNA（lncRNAs）作为各种人类疾病（包括癌症、神经退行性疾病和遗传疾病）的重要生物标志物和治疗靶点的研究取得进展，越来越多的证据凸显了它们在胃癌（GC）发生发展中的调控作用。然而，这些功能背后的机制在很大程度上仍不清楚。在本研究中，我们调查了LINC01048在GC细胞系（如HGC27和MKN45）的肿瘤发生和细胞增殖中的作用。对公开可用数据库的分析和实验验证表明，LINC01048在GC组织和细胞系中的表达升高，且与预后不良相关。敲低LINC01048可显著抑制GC细胞的增殖并诱导其凋亡。此外，LINC01048的缺失减少了β-连环蛋白的核定位，同时增加了其在细胞质中的滞留。此外，用Wnt/β-连环蛋白途径激活剂SKL2001处理可逆转LINC01048敲低对细胞增殖和凋亡的影响。体内实验证实，LINC01048的缺失可减少GC异种移植模型中的肿瘤生长。总体而言，这些发现表明LINC01048通过促进细胞增殖和调节Wnt/β-连环蛋白途径在GC中发挥致癌作用。因此，LINC01048可能作为GC治疗的潜在靶点。
