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综合泛癌基因组分析揭示了SLC30A5在肝细胞癌增殖、转移及预后中的作用。

Integrated pan-cancer genomic analysis reveals the role of SLC30A5 in the proliferation, metastasis, and prognosis of hepatocellular carcinoma.

作者信息

Liu Yihan, Lu Tong, Li Runze, Cui Long, Xu Rui, Teng Shenyi, Baranenko Denis, Zhang Tianze, Yang Lida, Qie Rui, Xiao Dan

机构信息

Graduate School, Heilongjiang University of Chinese Medicine, Harbin 150001, Heilongjiang, China.

Medical Technology Department, Qiqihar Medical University, Qiqihar 161006, Heilongjiang, China.

出版信息

J Cancer. 2024 Jul 2;15(14):4686-4699. doi: 10.7150/jca.97214. eCollection 2024.

DOI:10.7150/jca.97214
PMID:39006068
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11242337/
Abstract

SLC30A5, a member of the solute transporter protein family, is implicated in tumorigenesis and cancer progression. This study aimed to explore the expression and prognostic significance of SLC30A family genes in pan-cancer, with a specific emphasis on SLC30A5 in hepatocellular carcinoma (HCC). Expression patterns and prognostic implications of SLC30A family genes were assessed across 33 cancer types, especially HCC. Co-expression analysis explored the relationship between SLC30A5 and immune cell infiltration, immune checkpoints, pathway molecules related to tumor angiogenesis and epithelial-mesenchymal transition (EMT). The role of SLC30A5 in HCC was evaluated through and assays, including CCK8 viability assay, EdU cell proliferation assay, colony formation assay, apoptosis assay, wound healing assay, transwell migration assay, and xenograft mouse model assay using Huh7 cells with targeted knockdown of SLC30A5. SLC30A family genes exhibited overexpression in various tumors. In HCC, upregulation of SLC30A5 expression correlated with adverse prognosis. Significant associations were observed between SLC30A5 expression and immune cell infiltration, immune checkpoints, molecules involved in angiogenesis, and EMT. SLC30A5 overexpression was associated with advanced disease stages, higher histological grades, and vascular invasion. Single-cell RNA sequencing data (GSE112271) revealed notable SLC30A5 expression in malignant cells. and assays demonstrated that SLC30A5 knockdown in Huh7 cells reduced proliferation, migration, and invasion while promoting apoptosis. This study highlights the clinical relevance of SLC30A5 in HCC, emphasizing its role in cell proliferation and migration. SLC30A5 emerges as a promising candidate for a prognostic marker and a potential target in HCC.

摘要

溶质转运蛋白家族成员SLC30A5与肿瘤发生和癌症进展有关。本研究旨在探讨SLC30A家族基因在泛癌中的表达及预后意义,特别关注肝细胞癌(HCC)中的SLC30A5。评估了SLC30A家族基因在33种癌症类型(尤其是HCC)中的表达模式和预后意义。共表达分析探讨了SLC30A5与免疫细胞浸润、免疫检查点、肿瘤血管生成相关通路分子以及上皮-间质转化(EMT)之间的关系。通过CCK8活力测定、EdU细胞增殖测定、集落形成测定、凋亡测定、伤口愈合测定、Transwell迁移测定以及使用靶向敲低SLC30A5的Huh7细胞的异种移植小鼠模型测定,评估了SLC30A5在HCC中的作用。SLC30A家族基因在各种肿瘤中均表现出过表达。在HCC中,SLC30A5表达上调与不良预后相关。观察到SLC30A5表达与免疫细胞浸润、免疫检查点、血管生成相关分子以及EMT之间存在显著关联。SLC30A5过表达与疾病晚期、更高的组织学分级和血管侵犯相关。单细胞RNA测序数据(GSE112271)显示恶性细胞中SLC30A5有显著表达。CCK8活力测定和EdU细胞增殖测定表明,敲低Huh7细胞中的SLC30A5可降低细胞增殖、迁移和侵袭,同时促进细胞凋亡。本研究强调了SLC30A5在HCC中的临床相关性,突出了其在细胞增殖和迁移中的作用。SLC30A5有望成为HCC预后标志物的候选者和潜在靶点。

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J Hepatol. 2024 Jan;80(1):82-98. doi: 10.1016/j.jhep.2023.10.006. Epub 2023 Oct 12.
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Inhibition of TRPV4 remodels single cell polarity and suppresses the metastasis of hepatocellular carcinoma.抑制 TRPV4 重塑单细胞极性并抑制肝癌的转移。
Cell Death Dis. 2023 Jun 28;14(6):379. doi: 10.1038/s41419-023-05903-z.
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Tumor microenvironment signaling and therapeutics in cancer progression.
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Cancer Commun (Lond). 2023 May;43(5):525-561. doi: 10.1002/cac2.12416. Epub 2023 Apr 2.
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Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma.肿瘤微环境介导的肝细胞癌免疫逃逸。
Front Immunol. 2023 Feb 10;14:1133308. doi: 10.3389/fimmu.2023.1133308. eCollection 2023.
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Cancer Cell. 2023 Mar 13;41(3):404-420. doi: 10.1016/j.ccell.2023.01.010. Epub 2023 Feb 16.
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