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长链非编码RNA NEAT1通过调控CBX7和RTCB促进乳腺癌细胞的增殖、侵袭和迁移。

lncRNA NEAT1 Facilitates Cell Proliferation, Invasion and Migration by Regulating CBX7 and RTCB in Breast Cancer.

作者信息

Yan Lixia, Zhang Ze, Yin Xingmei, Li Yongxia

机构信息

Department of Breast and Thyroid Surgery, Dongying People's Hospital, Dongying, Shandong 257091, People's Republic of China.

Department of Stomatology and Eye, Dongying People's Hospital, Dongying, Shandong 257091, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Mar 24;13:2449-2458. doi: 10.2147/OTT.S240769. eCollection 2020.

Abstract

PURPOSE

To investigate the association between the lncRNA NEAT1 and breast cancer, and to determine the influence of NEAT1 on regulation of other signaling molecules in breast cancer.

METHODS

In the present study, we measured levels of the lncRNA NEAT1 in 106 breast cancer patients and in a human breast cancer cell line by qRT-PCR. The correlation between NEAT1 expression and patients' clinical characteristics was analyzed with in-house and TCGA data. We used cellular functioning assays and cell immunofluorescence assay to evaluate the role of NEAT1 and its target molecules in proliferation, invasion and migration in breast cancer. We used Western blotting to explore possible targets of NEAT1 and a subcellular fractionation assay to locate NEAT1 expression.

RESULTS

NEAT1 was overexpressed in breast cancer tissue and also closely related to advanced clinical stages and positive lymph node metastases. NEAT1 levels were also tightly correlated to prognosis for breast cancer patients in survival analyses. Cellular function assays revealed that downregulation of NEAT1 could inhibit breast cancer cell viability, invasion and migration. Western blotting revealed down-regulation of CBX7 and up-regulation of RTCB following NEAT1 inhibition. Based on the cytoplasmic and nuclear expression of NEAT1, we investigated the possible regulation of CBX7 and RTCB by NEAT1. Results showed that NEAT1 regulated the expression of CBX7 and RTCB, possibly by binding of NEAT1 to DNA in the nucleus, which facilitates cell proliferation, invasion and migration.

CONCLUSION

The current results suggest that the lncRNA NEAT1 is upregulated in breast cancer and facilitates tumor cell viability, invasion and migration via CBX7 and RTCB.

摘要

目的

研究长链非编码RNA NEAT1与乳腺癌之间的关联,并确定NEAT1对乳腺癌中其他信号分子调控的影响。

方法

在本研究中,我们通过qRT-PCR检测了106例乳腺癌患者及人乳腺癌细胞系中长链非编码RNA NEAT1的水平。利用内部数据和TCGA数据,分析NEAT1表达与患者临床特征之间的相关性。我们使用细胞功能测定和细胞免疫荧光测定来评估NEAT1及其靶分子在乳腺癌增殖、侵袭和迁移中的作用。我们使用蛋白质免疫印迹法探索NEAT1可能的靶标,并通过亚细胞分级分离测定来定位NEAT1的表达。

结果

NEAT1在乳腺癌组织中过表达,并且与晚期临床分期和阳性淋巴结转移密切相关。在生存分析中,NEAT1水平也与乳腺癌患者的预后密切相关。细胞功能测定显示,NEAT1的下调可抑制乳腺癌细胞的活力、侵袭和迁移。蛋白质免疫印迹法显示,NEAT1抑制后,CBX7表达下调,RTCB表达上调。基于NEAT1在细胞质和细胞核中的表达,我们研究了NEAT1对CBX7和RTCB的可能调控。结果表明,NEAT1可能通过在细胞核中与DNA结合来调控CBX7和RTCB的表达,从而促进细胞增殖、侵袭和迁移。

结论

目前的结果表明,长链非编码RNA NEAT1在乳腺癌中上调,并通过CBX7和RTCB促进肿瘤细胞的活力、侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/220d/7102915/f45946cf24ce/OTT-13-2449-g0001.jpg

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