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RNA结合蛋白RNPC1:在乳腺癌中作为一种肿瘤抑制因子发挥作用。

RNA-binding protein RNPC1: acting as a tumor suppressor in breast cancer.

作者信息

Xue Jin-Qiu, Xia Tian-Song, Liang Xiu-Qing, Zhou Wenbin, Cheng Lin, Shi Liang, Wang Ying, Ding Qiang

机构信息

Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.

出版信息

BMC Cancer. 2014 May 7;14:322. doi: 10.1186/1471-2407-14-322.

Abstract

BACKGROUND

RNA binding proteins (RBPs) play a fundamental role in posttranscriptional control of gene expression. Different RBPs have oncogenic or tumor-suppressive functions on human cancers. RNPC1 belongs to the RNA recognition motif (RRM) family of RBPs, which could regulate expression of diverse targets by mRNA stability in human cancer cells. Several studies reported that RNPC1 played an important role in cancer, mostly acting as an oncogene or up-regulating in tumors. However, its role in human breast cancer remains unclear.

METHODS

In the present study, we investigated the functional and mechanistic roles of RNPC1 in attenuating invasive signal including reverse epithelial-mesenchymal transition (EMT) to inhibit breast cancer cells aggressiveness in vitro. Moreover, RNPC1 suppress tumorigenicity in vivo. Further, we studied the expression of RNPC1 in breast cancer tissue and adjacent normal breast tissue by quantitative RT-PCR (qRT-PCR) and Western blot.

RESULTS

We observed that RNPC1 expression was silenced in breast cancer cell lines compared to breast epithelial cells. More important, RNPC1 was frequently silenced in breast cancer tissue compared to adjacent normal breast tissue. Low RNPC1 mRNA expression was associated with higher clinical stages and mutp53, while low level of RNPC1 protein was associated with higher lymph node metastasis, mutp53 and lower progesterone receptor (PR). Functional assays showed ectopic expression of RNPC1 could inhibit breast tumor cell proliferation in vivo and in vitro through inducing cell cycle arrest, and further suppress tumor cell migration and invasion partly through repressing mutant p53 (mutp53) induced EMT.

CONCLUSIONS

Overall, our findings indicated that RNPC1 had a potential function to play a tumor-suppressor role which may be a potential marker in the therapeutic and prognostic of breast cancer.

摘要

背景

RNA结合蛋白(RBPs)在基因表达的转录后调控中发挥着重要作用。不同的RBPs对人类癌症具有致癌或抑癌功能。RNPC1属于RBPs的RNA识别基序(RRM)家族,其可通过调节人类癌细胞中mRNA的稳定性来调控多种靶标的表达。多项研究报道,RNPC1在癌症中发挥重要作用,主要作为癌基因或在肿瘤中上调表达。然而,其在人类乳腺癌中的作用仍不清楚。

方法

在本研究中,我们研究了RNPC1在减弱侵袭信号(包括逆转上皮-间质转化(EMT))以抑制乳腺癌细胞体外侵袭性方面的功能和机制作用。此外,RNPC1在体内抑制肿瘤发生。进一步,我们通过定量逆转录-聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法研究了RNPC1在乳腺癌组织和相邻正常乳腺组织中的表达。

结果

我们观察到,与乳腺上皮细胞相比,乳腺癌细胞系中RNPC1的表达沉默。更重要的是,与相邻正常乳腺组织相比,RNPC1在乳腺癌组织中经常沉默。RNPC1 mRNA低表达与更高的临床分期和突变型p53相关,而RNPC1蛋白低水平与更高的淋巴结转移、突变型p53和更低的孕激素受体(PR)相关。功能分析表明,RNPC1的异位表达可通过诱导细胞周期停滞在体内和体外抑制乳腺肿瘤细胞增殖,并通过抑制突变型p53(mutp53)诱导的EMT进一步抑制肿瘤细胞迁移和侵袭。

结论

总体而言,我们的研究结果表明,RNPC1具有发挥肿瘤抑制作用的潜在功能,这可能是乳腺癌治疗和预后的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8682/4101826/5f818969e977/1471-2407-14-322-1.jpg

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