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miR-15b 通过抑制肿瘤抑制因子 PAQR3 促进乳腺癌的进展。

MiR-15b facilitates breast cancer progression via repressing tumor suppressor PAQR3.

机构信息

Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Jan;24(2):740-748. doi: 10.26355/eurrev_202001_20054.

Abstract

OBJECTIVE

Recently, breast cancer (BC) has become a common tumor that threatens the physical and mental health of women. Microribonucleic acids (miRNAs) have been chosen as a study object because of their roles in various cancers, including BC. Here, we mainly study the role of miR-15b in BC progression and its underlying mechanism.

PATIENTS AND METHODS

Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the level of MiR-15b expression in 60 pairs of BC tissues and para-cancerous specimens, and the relationship between MiR-15b level and clinical features of BC patient prognosis was analyzed. MiR-15b and PAQR3 level in BC tissues and cells was tested by Western blot.

RESULTS

The results showed that miR-15b expression was higher and PAQR3 level was lower in BC. The identification of PAQR3 as a target of miR-15b in BC was carried out by Luciferase reporter assay and the results stated that the Luciferase activity was reduced by miR-15b mimic, indicating PAQR3 being a target of miR-15b in BC. Transwell assay was used for examining BC cell migration and invasion and found that miR-15b could promote BC cell migration and invasion, while the effect of PAQR3 was inhibition. Furthermore, PAQR3 could reverse the promotion effect of miR-15b on BC cell migratory and invasive ability. In addition, miR-15b expression was negatively correlated with PAQR3 performed by regression analysis.

CONCLUSIONS

Our data stated that miR-15b could facilitate BC progression via repressing tumor suppressor PAQR3, indicating that miR-15b/PAQR3 axis provided a therapeutic target for treating BC.

摘要

目的

最近,乳腺癌(BC)已成为一种常见的肿瘤,威胁着女性的身心健康。微小 RNA(miRNAs)因其在包括 BC 在内的各种癌症中的作用而被选为研究对象。在这里,我们主要研究 miR-15b 在 BC 进展中的作用及其潜在机制。

患者和方法

通过定量实时聚合酶链反应(qRT-PCR)检测 60 对 BC 组织和癌旁标本中 miR-15b 的表达水平,并分析 miR-15b 水平与 BC 患者预后临床特征的关系。通过 Western blot 检测 BC 组织和细胞中的 miR-15b 和 PAQR3 水平。

结果

结果表明,miR-15b 在 BC 中的表达较高,PAQR3 水平较低。通过荧光素酶报告基因检测证实了 PAQR3 是 miR-15b 在 BC 中的靶标,结果表明 miR-15b 模拟物降低了荧光素酶活性,表明 PAQR3 是 miR-15b 在 BC 中的靶标。通过 Transwell assay 检测 BC 细胞迁移和侵袭发现,miR-15b 可促进 BC 细胞迁移和侵袭,而 PAQR3 的作用则抑制迁移和侵袭。此外,PAQR3 可逆转 miR-15b 对 BC 细胞迁移和侵袭能力的促进作用。此外,通过回归分析发现 miR-15b 表达与 PAQR3 呈负相关。

结论

我们的数据表明,miR-15b 可以通过抑制肿瘤抑制因子 PAQR3 促进 BC 的进展,表明 miR-15b/PAQR3 轴为治疗 BC 提供了一个治疗靶点。

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