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微小 RNA-27a 通过靶向三阴性乳腺癌中的 AKT 促进肿瘤发生。

MicroRNA‑27a promotes tumorigenesis via targeting AKT in triple negative breast cancer.

机构信息

Daytime Observation Ward, The First Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.

出版信息

Mol Med Rep. 2018 Jan;17(1):562-570. doi: 10.3892/mmr.2017.7886. Epub 2017 Oct 26.

DOI:10.3892/mmr.2017.7886
PMID:29115608
Abstract

Altered microRNA (miRNA/miR) expression regulates tumor development and progression in triple‑negative breast cancer (TNBC). The present study examined the effect of miR‑27a on proliferation, migration and invasion of TNBC cells in vitro and in vivo. An MTT assay was performed to examine the proliferation of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells with either overexpression of miR‑27a or downregulation of miR‑27a, in the presence or absence of radiation. The migratory and invasive abilities of MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells were assessed by Transwell migration and Matrigel invasion assays. The protein expression levels were examined by western blotting. The caspase‑Glo3/7 assay was performed to examine the effect of miR‑27a on radiation‑induced apoptosis in MDA‑MB‑231 and MDA‑MB‑468 breast cancer cells. A luciferase assay was performed to evaluate the effect of miR‑27a on phosphatase and tensin homolog (PTEN) and B cell lymphoma (Bcl)‑2 associated X, apoptosis regulator (BAX) expression. Immunodeficient nude mice were used to examine tumor growth following injection of MDA‑MB‑231 breast cancer cells. miR‑27a promoted proliferation in vitro and in vivo, and enhanced migration and invasion in TNBC cells. miR‑27a improved the survival of TNBC cells following irradiation. miR‑27a inhibited radiation‑induced apoptosis in TNBC cells by regulation of caspase 3/7 and Bcl‑2 expression. Furthermore, the expression levels of PTEN and phosphorylated protein kinase B in MDA‑MB‑231 and MDA‑MB‑468 cells was altered following overexpression of miR‑27a. The luciferase assay demonstrated that miR‑27a regulated PTEN and BAX expression by binding to 3'‑untranslated regions. Overall, miR‑27a exhibits an essential role in tumor development and progression in TNBC and may be used as a potential biomarker to predict radiotherapy response and prognosis for the disease.

摘要

miRNA(miR/miRNA)表达的改变调控三阴性乳腺癌(TNBC)的肿瘤发生和发展。本研究检测了 miR-27a 对 TNBC 细胞在体外和体内增殖、迁移和侵袭的影响。采用 MTT 法检测过表达 miR-27a 或下调 miR-27a 后,在存在或不存在辐射的情况下 MDA-MB-231 和 MDA-MB-468 乳腺癌细胞的增殖情况。通过 Transwell 迁移和 Matrigel 侵袭实验评估 MDA-MB-231 和 MDA-MB-468 乳腺癌细胞的迁移和侵袭能力。通过 Western blot 检测蛋白表达水平。采用 caspase-Glo3/7 实验检测 miR-27a 对 MDA-MB-231 和 MDA-MB-468 乳腺癌细胞辐射诱导凋亡的影响。采用荧光素酶实验评估 miR-27a 对磷酸酶和张力蛋白同源物(PTEN)和 B 细胞淋巴瘤(Bcl)-2 相关 X,凋亡调节因子(BAX)表达的影响。免疫缺陷裸鼠用于注射 MDA-MB-231 乳腺癌细胞后观察肿瘤生长情况。miR-27a 促进 TNBC 细胞在体外和体内的增殖,并增强其迁移和侵袭能力。miR-27a 改善了 TNBC 细胞在照射后的存活率。miR-27a 通过调控 caspase 3/7 和 Bcl-2 表达抑制 TNBC 细胞的辐射诱导凋亡。此外,过表达 miR-27a 后 MDA-MB-231 和 MDA-MB-468 细胞中 PTEN 和磷酸化蛋白激酶 B 的表达水平发生改变。荧光素酶实验表明,miR-27a 通过与 3'-UTR 结合调节 PTEN 和 BAX 表达。总的来说,miR-27a 在 TNBC 的肿瘤发生和发展中发挥重要作用,可能作为预测疾病放疗反应和预后的潜在生物标志物。

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