Laboratory of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
J Biochem Mol Toxicol. 2024 Aug;38(8):e23774. doi: 10.1002/jbt.23774.
Colorectal cancer (CRC) is a common gastrointestinal malignancy. Long noncoding RNAs (lncRNAs) are associated with the progression of various cancers, including CRC. Herein, we explored the function of lncRNA LINC01550 in CRC. LINC01550 expression in CRC was analyzed using The Cancer Genome Atlas (TCGA). The diagnostic value of LINC01550 was evaluated using ROC curves. The relationship between clinicopathological variables and LINC01550 expression was explored, and its prognostic value was assessed using Kaplan-Meier and Cox regression analyses. The relationship between LINC01550 expression and immune cell infiltration was analyzed using CIBERSORT. Tumor-associated mutations and drug sensitivity were compared between high and low LINC01550 expression groups. The effects of LINC01550 overexpression on CRC cells were investigated using CCK-8, flow cytometry, wound healing, Transwell, qRT-PCR, and western blot assays. LINC01550 was downregulated in CRC tissues, and the low expression of LINC01550 was correlated with advanced stage and metastasis. CRC patients with low LINC01550 expression had poorer overall survival. LINC01550 expression was an independent risk factor for CRC prognosis. APC and TP53 mutations were more frequent in the low LINC01550 expression group, while the high LINC01550 expression group was significantly more sensitive to 5-fluorouracil, irinotecan, trametinib, gemcitabine, rapamycin, and XAV939. LINC01550 overexpression suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition of HCT-116 and HT-29 cells and promoted apoptosis. LINC01550 exerted these effects by inhibiting Wnt/β-catenin signaling. Our results suggest LINC01550 as a diagnostic and prognostic predictor in CRC that acts as a tumor suppressor and a potential therapeutic target.
结直肠癌(CRC)是一种常见的胃肠道恶性肿瘤。长链非编码 RNA(lncRNA)与包括 CRC 在内的多种癌症的进展有关。本文探讨了 lncRNA LINC01550 在 CRC 中的功能。使用癌症基因组图谱(TCGA)分析 CRC 中 LINC01550 的表达。使用 ROC 曲线评估 LINC01550 的诊断价值。探讨临床病理变量与 LINC01550 表达的关系,并通过 Kaplan-Meier 和 Cox 回归分析评估其预后价值。使用 CIBERSORT 分析 LINC01550 表达与免疫细胞浸润的关系。比较高低 LINC01550 表达组之间的肿瘤相关突变和药物敏感性。使用 CCK-8、流式细胞术、划痕愈合、Transwell、qRT-PCR 和 Western blot 检测 LINC01550 过表达对 CRC 细胞的影响。LINC01550 在 CRC 组织中下调,LINC01550 低表达与晚期和转移相关。LINC01550 低表达的 CRC 患者总生存期较差。LINC01550 表达是 CRC 预后的独立危险因素。APC 和 TP53 突变在 LINC01550 低表达组中更为频繁,而 LINC01550 高表达组对 5-氟尿嘧啶、伊立替康、曲美替尼、吉西他滨、雷帕霉素和 XAV939 更为敏感。LINC01550 过表达抑制 HCT-116 和 HT-29 细胞的增殖、迁移、侵袭和上皮-间充质转化,并促进凋亡。LINC01550 通过抑制 Wnt/β-catenin 信号通路发挥这些作用。我们的研究结果表明,LINC01550 作为 CRC 的诊断和预后预测指标,发挥肿瘤抑制作用,是潜在的治疗靶点。