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微小RNA-20b在原发性乳腺癌脑转移灶中表达上调。

miR-20b is up-regulated in brain metastases from primary breast cancers.

作者信息

Ahmad Aamir, Ginnebaugh Kevin R, Sethi Seema, Chen Wei, Ali Rouba, Mittal Sandeep, Sarkar Fazlul H

机构信息

Department of Pathology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.

Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, Michigan, USA.

出版信息

Oncotarget. 2015 May 20;6(14):12188-95. doi: 10.18632/oncotarget.3664.

Abstract

Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.

摘要

脑转移在晚期乳腺癌患者中很常见,且与预后不良相关。然而,尚未建立独特的分子生物标志物。我们假设微小RNA-20b(miR-20b)在乳腺癌脑转移中起作用。我们的研究队列包括11例有脑转移的乳腺癌患者和9例对照患者(年龄、分期和随访匹配),这些对照患者患有无脑转移的乳腺癌。对病例进行显微镜检查,以选择肿瘤细胞>50%的肿瘤组织块,从福尔马林固定石蜡包埋(FFPE)肿瘤组织块中提取RNA,并使用qRT-PCR分析miR-20b的表达。我们进一步使用MCF-7和MDA-MB-231细胞在体外测试了miR-20b过表达对集落形成和侵袭的影响。在患者来源的样本中,与原发性乳腺肿瘤以及无脑转移的患者相比,乳腺癌患者脑转移灶中miR-20b的表达显著更高。miR-20b还显著诱导了乳腺癌细胞的集落形成和侵袭性。此外,与骨转移细胞相比,在脑转移细胞中观察到miR-20b水平较高。总之,我们的研究结果表明miR-20b在乳腺癌脑转移中具有新的作用,其作为预后和/或治疗靶点的潜力值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2c/4494931/bb4bb014a4a6/oncotarget-06-12188-g001.jpg

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