RNA-binding protein RNPC1: acting as a tumor suppressor in breast cancer.
RNA-binding protein RNPC1: acting as a tumor suppressor in breast cancer.
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RNA结合蛋白RNPC1：在乳腺癌中充当肿瘤抑制因子
DOI：
10.1186/1471-2407-14-322
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发表时间：
2014-05-07
期刊：
影响因子：
3.8
通讯作者：
Ding Q
中科院分区：
文献类型：
--
作者：
Xue JQ;Xia TS;Liang XQ;Zhou W;Cheng L;Shi L;Wang Y;Ding Q
研究背景RNA结合蛋白（RNA binding proteins，RBP）在基因表达的转录后调控中起着重要作用。RNPC 1属于RBP的RNA识别基序（RNA recognition motif，RRM）家族，在人癌细胞中通过mRNA的稳定性调控多种靶点的表达。一些研究报道RNPC 1在癌症中发挥重要作用，主要作为癌基因或在肿瘤中上调。然而，它在人类乳腺癌中的作用仍然不清楚。MethodsIn本研究中，我们研究RNPC 1在减弱侵袭性信号，包括逆转上皮间质转化（EMT），以抑制乳腺癌细胞的侵袭性在体外的功能和机制的作用。RNPC 1在体内具有抑制肿瘤发生的作用。此外，我们研究了RNPC 1在乳腺癌组织和癌旁正常乳腺组织中的表达，通过定量RT-PCR（qRT-PCR）和Western blot.ResultsWe观察到，RNPC 1表达沉默的乳腺癌细胞系相比，乳腺上皮细胞。更重要的是，与邻近的正常乳腺组织相比，RNPC 1在乳腺癌组织中经常沉默。RNPC 1 mRNA表达水平低与临床分期高、mutp 53高相关，RNPC 1蛋白表达水平低与淋巴结转移高、mutp 53高、孕酮受体（PR）低相关。功能分析显示RNPC 1的异位表达可通过诱导细胞周期阻滞抑制乳腺癌细胞在体内和体外的增殖，并通过抑制突变型p53（mutp 53）诱导的EMT进一步抑制肿瘤细胞的迁移和侵袭。我们的研究结果表明RNPC 1有一个潜在的功能，发挥肿瘤-可能是乳腺癌治疗和预后的潜在标志物。
BackgroundRNA binding proteins (RBPs) play a fundamental role in posttranscriptional control of gene expression. Different RBPs have oncogenic or tumor-suppressive functions on human cancers.RNPC1belongs 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.MethodsIn 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 aggressivenessin vitro. Moreover, RNPC1 suppress tumorigenicityin 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.ResultsWe 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 proliferationin vivoandin vitrothrough inducing cell cycle arrest, and further suppress tumor cell migration and invasion partly through repressing mutant p53 (mutp53) induced EMT.ConclusionsOverall, 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.
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