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miR-934 通过调控 PTEN 和上皮间质转化促进乳腺癌转移。

miR-934 promotes breast cancer metastasis by regulation of PTEN and epithelial-mesenchymal transition.

机构信息

Department of Clinical Laboratory, Huai'an Maternity and Child Health Care Hospital, Huai'an, China.

School of Medical Technology, Jiangsu College of Nursing, Huai'an, China.

出版信息

Tissue Cell. 2021 Aug;71:101581. doi: 10.1016/j.tice.2021.101581. Epub 2021 Jun 11.

Abstract

Breast cancer (BC) is the most commonly diagnosed malignancy and the leading cause of cancer-related mortality among females. Over 90 % of the cases of death in BC patients are attributed to tumor cell metastasis. Therefore, it is urgently needed to investigate the molecular mechanisms of BC metastasis. The expression of miRNA in BC was evaluated by qRT-PCR and bioinformatics analysis. Clone formation, EdU assays, and subcutaneous xenograft model were used to test the growth of BC cells. Wound healing, transwell assays, and lung-metastasis model were used to explore the effect of miR-934 knockdown on cell metastasis. The miR-934 targets in BC were identified through bioinformatics analysis and luciferase reporter assays. The expression of protein was tested by western blot. The binding of mRNA and RNA-binding-protein was verified using RIP assays. miR-934 expression was significantly elevated in BC tissues, especially in those with lymph node metastasis and associated with poor patient prognosis. Experiments in vitro and in vivo showed that that upregulated miR-934 was not necessarily required for the growth of BC cells. However, miR-934 knockdown significantly inhibited the migration and invasion abilities of BC cells. Moreover, PTEN as identified as the direct target of miR-934 in BC, and miR-934 could promote BC cell metastasis by regulation of PTEN and epithelial-mesenchymal transition (EMT). Our results suggested that targeting miR-934 may be a practical treatment for BC cell metastasis.

摘要

乳腺癌(BC)是最常见的恶性肿瘤,也是女性癌症相关死亡的主要原因。超过 90%的 BC 患者的死亡归因于肿瘤细胞转移。因此,迫切需要研究 BC 转移的分子机制。通过 qRT-PCR 和生物信息学分析评估了 miRNA 在 BC 中的表达。克隆形成、EdU 检测和皮下异种移植模型用于检测 BC 细胞的生长。伤口愈合、Transwell 检测和肺转移模型用于研究 miR-934 敲低对细胞转移的影响。通过生物信息学分析和荧光素酶报告基因检测鉴定了 BC 中的 miR-934 靶标。通过 Western blot 检测蛋白表达。使用 RIP 检测验证 mRNA 和 RNA 结合蛋白的结合。miR-934 在 BC 组织中表达明显上调,尤其是在有淋巴结转移的组织中,并与患者预后不良相关。体外和体内实验表明,BC 细胞的生长并不一定需要上调 miR-934。然而,miR-934 敲低显著抑制了 BC 细胞的迁移和侵袭能力。此外,PTEN 被鉴定为 BC 中 miR-934 的直接靶标,miR-934 通过调节 PTEN 和上皮间质转化(EMT)促进 BC 细胞转移。我们的研究结果表明,靶向 miR-934 可能是治疗 BC 细胞转移的一种实用方法。

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