长非编码 RNA LINC01550 通过抑制 Wnt/β-catenin 信号通路抑制结直肠癌恶变

IF 3.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biochemical and Molecular Toxicology Pub Date : 2024-07-23 DOI:10.1002/jbt.23774
Weiyun Wu, Aiting Li, Huanjin He, Shicai Ye, Zhuliang Zhou, Juan-Hua Quan, Wenkai Tan
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引用次数: 0

摘要

大肠癌(CRC)是一种常见的胃肠道恶性肿瘤。长非编码 RNA(lncRNA)与包括 CRC 在内的多种癌症的进展相关。在此,我们探讨了lncRNA LINC01550在CRC中的功能。我们利用癌症基因组图谱(TCGA)分析了LINC01550在CRC中的表达。利用ROC曲线评估了LINC01550的诊断价值。探讨了临床病理变量与LINC01550表达之间的关系,并使用Kaplan-Meier和Cox回归分析评估了其预后价值。利用CIBERSORT分析了LINC01550表达与免疫细胞浸润之间的关系。比较了LINC01550高表达组和低表达组的肿瘤相关突变和药物敏感性。利用CCK-8、流式细胞术、伤口愈合、Transwell、qRT-PCR和Western印迹检测法研究了LINC01550过表达对CRC细胞的影响。LINC01550在CRC组织中下调,LINC01550的低表达与晚期和转移相关。LINC01550低表达的CRC患者总生存率较低。LINC01550的表达是影响CRC预后的一个独立危险因素。LINC01550低表达组中APC和TP53突变更常见,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的敏感性明显更高。LINC01550的过表达抑制了HCT-116和HT-29细胞的增殖、迁移、侵袭和上皮-间质转化,并促进了细胞凋亡。LINC01550通过抑制Wnt/β-catenin信号转导发挥这些作用。我们的研究结果表明,LINC01550可作为一种肿瘤抑制因子和潜在的治疗靶点,预测CRC的诊断和预后。
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Long noncoding RNA LINC01550 inhibits colorectal cancer malignancy by suppressing the Wnt/β-catenin signaling pathway

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.

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来源期刊
CiteScore
5.80
自引率
2.80%
发文量
277
审稿时长
6-12 weeks
期刊介绍: The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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