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上调 IncRNA WTAPP1 在三阴性乳腺癌中预测生存。

Upregulated IncRNA WTAPP1 in Triple Negative Breast Cancer Predicts Survival.

机构信息

Department of Oncology, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an City, Shanxi Province, 710004, P.R. China.

出版信息

Crit Rev Eukaryot Gene Expr. 2022;32(1):67-78. doi: 10.1615/CritRevEukaryotGeneExpr.2021039983.

Abstract

The migration and angiogenesis of endothelial progenitor cells require the involvement of WTAPP1. Cell migration and angiogenesis are critical for cancer development, we therefore speculated that WTAPP1 may participate in cancer biology. This study aimed to explore the role of WTAPP1 in triple-negative breast cancer (TNBC). A total of 68 patients (females, 38 to 67 years old, mean age 52.1 ± 5.9 years old) were enrolled in this study. The effects of over-expression of WTAPP1 and miR-34a on EEF2K were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Transient cell transfections were performed to explore the interactions between genes. Cell proliferation assay was used to analyze cell proliferation. Transwell assays were performed to detect cell invasive and migration. Flow cytometry was used to evaluate apoptosis. WTAPP1 was upregulated in tumor tissues of TNBC patients and high expression levels of WTAPP1 in tumor tissues predicted poor survival. In contrast, miR-34a was downregulated in TNBC. Correlation analysis showed that WTAPP1 and miR-34a were negatively correlated with each other. In cancer cells, overexpression of WTAPP1 resulted in downregulation of miR-34a. Remarkably, overexpression of WTAPP1 increased the expression levels of EEF2K, a target of miR-34a. Overexpression of WTAPP1 and EEF2K increased proliferation, invasion and migration of TNBC cells, while overexpression of miR-34a showed different results. In addition, overexpression of miR-34a enhanced the effects of overexpression of WTAPP1 and EEF2K on apoptosis. WTAPP1 may promote TNBC cell proliferation by downregulating miR-34a.

摘要

内皮祖细胞的迁移和血管生成需要 WTAPP1 的参与。细胞迁移和血管生成对于癌症的发展至关重要,因此我们推测 WTAPP1 可能参与癌症生物学。本研究旨在探讨 WTAPP1 在三阴性乳腺癌 (TNBC) 中的作用。共纳入 68 例患者(女性,38-67 岁,平均年龄 52.1±5.9 岁)。通过逆转录定量聚合酶链反应 (RT-qPCR) 和 Western blot 评估 WTAPP1 和 miR-34a 过表达对 EEF2K 的影响。进行瞬时细胞转染以探索基因之间的相互作用。细胞增殖试验用于分析细胞增殖。Transwell 测定用于检测细胞侵袭和迁移。流式细胞术用于评估细胞凋亡。WTAPP1 在 TNBC 患者的肿瘤组织中上调,肿瘤组织中 WTAPP1 的高表达水平预示着预后不良。相比之下,miR-34a 在 TNBC 中下调。相关性分析表明 WTAPP1 和 miR-34a 相互负相关。在癌细胞中,WTAPP1 的过表达导致 miR-34a 的下调。值得注意的是,WTAPP1 的过表达增加了 miR-34a 的靶标 EEF2K 的表达水平。WTAPP1 和 EEF2K 的过表达增加了 TNBC 细胞的增殖、侵袭和迁移,而 miR-34a 的过表达则显示出不同的结果。此外,miR-34a 的过表达增强了 WTAPP1 和 EEF2K 过表达对细胞凋亡的影响。WTAPP1 可能通过下调 miR-34a 促进 TNBC 细胞的增殖。

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