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长链非编码RNA SPRY4-IT1通过上调ZNF703表达来增加人乳腺癌细胞的增殖。

The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression.

作者信息

Shi Yongguo, Li Juan, Liu Yangchen, Ding Jie, Fan Yingrui, Tian Yun, Wang Li, Lian Yifan, Wang Keming, Shu Yongqian

机构信息

Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.

Taixing People's Hospital, Taixing, Jiangsu, PR China.

出版信息

Mol Cancer. 2015 Feb 22;14:51. doi: 10.1186/s12943-015-0318-0.

DOI:10.1186/s12943-015-0318-0
PMID:25742952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4350857/
Abstract

BACKGROUND

Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes, such as cell growth and apoptosis. The SPRY4 intronic transcript 1 (SPRY4-IT1) is a 708-bp lncRNA on chromosome 5 with a potential functional role in tumorigenesis. The clinical significance of SPRY4-IT1 and the effect of SPRY4-IT1 on cancer progression are unclear.

METHODS

Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the expression of SPRY4-IT1 in 48 breast cancer tissues and four breast cancer cell lines. Gain and loss of function approaches were used to investigate the biological role of SPRY4-IT1 in vitro. Microarray bioinformatics analysis was performed to identify the putative targets of SPRY4-IT1, which were further verified by rescue experiments, and by western blotting and qRT-PCR.

RESULTS

SPRY4-IT1 expression was significantly upregulated in 48 breast cancer tumor tissues comparedwith normal tissues. Additionally, increased SPRY4-IT1 expression was found to be associated with a larger tumor size and an advanced pathological stage in breast cancer patients. The knockdown of SPRY4-IT1 significantly suppressed proliferation and caused apoptosis of breast cancer cells in vitro. Furthermore, we discovered that ZNF703 was a target of SPRY4-IT1 and was downregulated by SPRY4-IT1 knockdown. Moreover, we provide the first demonstration that ZNF703 plays an oncogenic role in ER (-) breast carcinoma cells.

CONCLUSIONS

SPRY4-IT1 is a novel prognostic biomarker and a potential therapeutic candidate for breast cancer.

摘要

背景

长链非编码RNA（lncRNAs）最近作为一类新的基因出现，可调节细胞生长和凋亡等细胞过程。SPRY4内含子转录本1（SPRY4-IT1）是位于5号染色体上的一个708个碱基对的lncRNA，在肿瘤发生中可能具有功能作用。SPRY4-IT1的临床意义以及SPRY4-IT1对癌症进展的影响尚不清楚。

方法

采用定量逆转录聚合酶链反应（qRT-PCR）检测48例乳腺癌组织和4种乳腺癌细胞系中SPRY4-IT1的表达。运用功能获得和功能缺失方法在体外研究SPRY4-IT1的生物学作用。进行微阵列生物信息学分析以鉴定SPRY4-IT1的假定靶点，通过挽救实验、蛋白质免疫印迹法和qRT-PCR进一步验证。

结果

与正常组织相比，48例乳腺癌肿瘤组织中SPRY4-IT1表达显著上调。此外，发现SPRY4-IT1表达增加与乳腺癌患者更大的肿瘤大小和更高的病理分期相关。敲低SPRY4-IT1可显著抑制体外乳腺癌细胞的增殖并诱导其凋亡。此外，我们发现ZNF703是SPRY4-IT1的一个靶点，敲低SPRY4-IT1可使其下调。而且，我们首次证明ZNF703在雌激素受体（ER）阴性乳腺癌细胞中发挥致癌作用。

结论

SPRY4-IT1是一种新型的乳腺癌预后生物标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/2f13eb95308b/12943_2015_318_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/c3bb0a3d95d4/12943_2015_318_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/313b40b84544/12943_2015_318_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/b75315c1bb1d/12943_2015_318_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/e3df2640dcd0/12943_2015_318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/dab221cea9e5/12943_2015_318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/2f13eb95308b/12943_2015_318_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/c3bb0a3d95d4/12943_2015_318_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/313b40b84544/12943_2015_318_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/b75315c1bb1d/12943_2015_318_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/e3df2640dcd0/12943_2015_318_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/dab221cea9e5/12943_2015_318_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41a/4350857/2f13eb95308b/12943_2015_318_Fig6_HTML.jpg

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