LncRNA UCA1 promotes vasculogenic mimicry by targeting miR-1-3p in gastric cancer.

IF 3.3 3区 医学 Q2 ONCOLOGY Carcinogenesis Pub Date : 2024-09-11 DOI:10.1093/carcin/bgae031
Yida Lu, Bo Yang, Aolin Shen, Kexun Yu, MengDi Ma, Yongxiang Li, Huizhen Wang
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Abstract

Long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been implicated in several tumors. UCA1 promotes cell proliferation, migration, and invasion of gastric cancer (GC) cells, but the molecular mechanism has not been fully elucidated. This study revealed the oncogenic effects of UCA1 on cell growth and invasion. Furthermore, UCA1 expression was significantly correlated with the overall survival of GC patients, and the clinicopathological indicators, including tumor size, depth of invasion, lymph node metastasis, and TNM stage. Additionally, miR-1-3p was identified as a downstream target of UCA1, which was negatively regulated by UCA1. MiR-1-3p inhibited cell proliferation and vasculogenic mimicry (VM), and induced cell apoptosis by upregulating BAX, BAD, and tumor suppressor TP53 expression levels. Moreover, miR-1-3p almost completely reversed the oncogenic effect caused by UCA1, including cell growth, migration, and VM formation. This study also confirmed that UCA1 promoted tumor growth in vivo. In this study, we also revealed the correlation between UCA1 and VM formation, which is potentially crucial for tumor metastasis. Meanwhile, its downstream target miR-1-3p inhibited VM formation in GC cells. In summary, these findings indicate that the UCA1/miR-1-3p axis is a potential target for GC treatment.

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LncRNA UCA1通过靶向miR-1-3p促进胃癌血管生成模拟。
长非编码 RNA(lncRNA)尿路上皮癌相关 1(UCA1)与多种肿瘤有关。UCA1 可促进 GC 细胞的增殖、迁移和侵袭,但其分子机制尚未完全阐明。本研究揭示了 UCA1 对细胞生长和侵袭的致癌作用。此外,UCA1的表达与GC患者的总生存期、临床病理指标(包括肿瘤大小、侵袭深度、淋巴结转移和TNM分期)显著相关。此外,miR-1-3p 被确定为 UCA1 的下游靶标,并受到 UCA1 的负调控。MiR-1-3p 可抑制细胞增殖和血管生成模拟(VM),并通过上调 BAX、BAD 和肿瘤抑制因子 TP53 的表达水平诱导细胞凋亡。此外,miR-1-3p 几乎完全逆转了 UCA1 的致癌作用,包括细胞生长、迁移和 VM 形成。这项研究还证实了 UCA1 在体内促进肿瘤生长的作用。在这项研究中,我们还发现了 UCA1 与 VM 形成之间的相关性,而 VM 的形成可能是肿瘤转移的关键。同时,其下游靶标 miR-1-3p 可抑制 GC 细胞中 VM 的形成。总之,这些研究结果表明,UCA1/miR-1-3p 轴是治疗 GC 的潜在靶点。
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来源期刊
Carcinogenesis
Carcinogenesis 医学-肿瘤学
CiteScore
9.20
自引率
2.10%
发文量
95
审稿时长
1 months
期刊介绍: Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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