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CLC number: R979.1

On-line Access: 2020-06-01

Received: 2019-10-07

Revision Accepted: 2020-03-10

Crosschecked: 2020-05-26

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Xi-Ping Zhang

https://orcid.org/0000-0002-3556-9681

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Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.6 P.495-508

http://doi.org/10.1631/jzus.B1900584


Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis


Author(s):  En-Qi Qiao, Hong-Jian Yang, Xi-Ping Zhang

Affiliation(s):  Department of Breast Surgery, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China

Corresponding email(s):   zxp99688@sina.com

Key Words:  Breast cancer (BC), Human epidermal growth factor receptor 2 (Her-2), Lymphatic metastasis, MicroRNA (miRNA), Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)


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En-Qi Qiao, Hong-Jian Yang, Xi-Ping Zhang. Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis[J]. Journal of Zhejiang University Science B, 2020, 21(6): 495-508.

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author="En-Qi Qiao, Hong-Jian Yang, Xi-Ping Zhang",
journal="Journal of Zhejiang University Science B",
volume="21",
number="6",
pages="495-508",
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%T Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis
%A En-Qi Qiao
%A Hong-Jian Yang
%A Xi-Ping Zhang
%J Journal of Zhejiang University SCIENCE B
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900584

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T1 - Screening of miRNAs associated with lymph node metastasis in Her-2-positive breast cancer and their relationship with prognosis
A1 - En-Qi Qiao
A1 - Hong-Jian Yang
A1 - Xi-Ping Zhang
J0 - Journal of Zhejiang University Science B
VL - 21
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EP - 508
%@ 1673-1581
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1900584


Abstract: 
The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2 (Her-2)-positive breast cancer (BC). We analyzed correlations between microRNAs (miRNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas (TCGA) database. The expression levels of miR-455, miR-143, and miR-99a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed miR-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of miR-455 was significantly and positively correlated to the prognosis and overall survival (OS) of the BC (P=0.028), according to TCGA information. The expression level of miR-455 was positively correlated with OS and relapse-free survival (RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes (P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive (P<0.01) after being transfected with miR-455 mimics. During the qRT-PCR, the expression level of MALAT1 declined significantly after transfection (P<0.01). Overexpressed miR-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that miR-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. miR-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.

Her-2阳性乳腺癌淋巴结转移相关的miRNA的筛选及其与患者预后关系的研究

目的:寻找一种或多种能预测人类表皮生长因子受体2(Her-2)阳性乳腺癌患者是否发生淋巴结转移及其预后的分子标志物.
创新点:本研究发现,miR-455与Her-2阳性乳腺癌转移相关,可能是一个预测Her-2阳性乳腺癌患者淋巴结转移和预后的分子标志物.miR-455可以通过与长链非编码RNA人肺腺癌转移相关转录本1(MALAT1)的相互作用,在乳腺癌的淋巴结转移过程中发挥重要功能.
方法:通过下载肿瘤基因组图谱(TCGA)数据库中与乳腺癌相关的微小RNA(miRNA)测序数据,筛选与乳腺癌淋巴结转移相关的miRNA,进一步分析这些miRNA与乳腺癌患者预后的相关性.同时,用实时荧光定量聚合酶链反应(qRT-PCR)方法检测这些miRNA在不同程度淋巴结转移的Her-2阳性乳腺癌患者组织中的表达水平,及其与预后的相关性.通过细胞学实验研究过表达miR-455对Her-2阳性乳腺癌细胞系MDA-MB-453增殖和侵袭能力的影响,并用qRT-PCR检测过表达miR-455对MALAT1表达的影响.
结论:miR-455可能是Her-2阳性乳腺癌患者淋巴结转移和预后的潜在预测因子.

关键词:乳腺癌;人表皮生长因子受体2(Her-2);淋巴结转移;微小RNA(miRNA);人肺腺癌转移相关转录本1(MALAT1)

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[72]List of electronic supplementary materials

[73]Table S1 Primer information of qRT-PCR

[74]Table S2 Sequence information of miRNA mimics

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