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RBM3 通过结合 3'UTR 而上调 ARPC2 的表达,促进乳腺癌的进展。

RBM3 upregulates ARPC2 by binding the 3'UTR and contributes to breast cancer progression.

机构信息

Zhongda Hospital Lishui Branch, Southeast University, Nanjing Lishui People's Hospital, Nanjing, Jiangsu 211200, P.R. China.

Medical School, Xiamen University, Xiamen, Fujian 361005, P.R. China.

出版信息

Int J Oncol. 2019 Apr;54(4):1387-1397. doi: 10.3892/ijo.2019.4698. Epub 2019 Jan 28.

Abstract

Breast cancer is one of the most common types of cancers which results in a high mortality rate for patients worldwide. In this study, we performed systematical experiments including tissue analysis (immunohistochemistry etc.) and cell functional experiments (cell counting assay, MTT assay, cell colony formation, cell migration assay, cell invasion assay etc.). We demonstrated that the expression level of RNA binding motif protein 3 (RBM3) was higher in human breast cancer tissues compared with adjacent non‑tumor tissues. A high level of RBM3 was associated with worse post‑operative relapse‑free survival (RFS) and overall survival (OS) rates in patients with breast cancer. Among the patients with breast cancer, the expression of RBM3 was associated with patient lymph node metastasis and a high tumor grade. The knockdown of RBM3 markedly decreased the proliferation and metastasis of human breast cancer cells. In downstream pathway analysis, actin related protein 2/3 complex subunit 2 (ARPC2) was determined to be positively regulated by RBM3 through a post‑transcriptional 3'UTR‑binding manner. ARPC2 also played an oncogenic role and mediated the promoting role of RBM3 in the proliferation and metastasis of human breast cancer cells. Thus, on the whole, the findings of this study demonstrate that RBM3 acts as an oncogene in human breast cancer cells and that the functional depletion of RBM3 may be considered as a potential method for breast cancer therapy.

摘要

乳腺癌是全球范围内导致患者死亡率较高的最常见癌症类型之一。在本研究中,我们进行了系统的实验,包括组织分析(免疫组织化学等)和细胞功能实验(细胞计数分析、MTT 分析、细胞集落形成、细胞迁移分析、细胞侵袭分析等)。我们证实,RNA 结合基序蛋白 3(RBM3)在人乳腺癌组织中的表达水平高于相邻非肿瘤组织。高水平的 RBM3 与乳腺癌患者术后无复发生存(RFS)和总生存(OS)率较差相关。在乳腺癌患者中,RBM3 的表达与患者淋巴结转移和高肿瘤分级相关。敲低 RBM3 显著降低了人乳腺癌细胞的增殖和转移。在下游通路分析中,确定肌动蛋白相关蛋白 2/3 复合物亚基 2(ARPC2)通过转录后 3'UTR 结合方式被 RBM3 正向调控。ARPC2 也发挥致癌作用,并介导 RBM3 在人乳腺癌细胞增殖和转移中的促进作用。因此,总的来说,本研究的结果表明,RBM3 是人乳腺癌细胞中的癌基因,功能性耗尽 RBM3 可能被视为乳腺癌治疗的一种潜在方法。

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