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肝再生磷酸酶-3 诱导的 miR-21、miR-17 和 miR-19a 促进结肠癌的增殖和转移。

miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer.

机构信息

Department of Hepatobiliary Surgery, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, China.

出版信息

Br J Cancer. 2012 Jul 10;107(2):352-9. doi: 10.1038/bjc.2012.251. Epub 2012 Jun 7.

Abstract

BACKGROUND

Phosphatase of regenerating liver-3 (PRL-3) is an oncogene known to promote tumour metastasis, especially in colorectal cancer (CRC). Here, we demonstrate that the miR-21, miR-17 and miR-19a expressions induced by PRL-3 are involved in the proliferation and metastasis of colon cancer.

METHODS

Microarray analysis and quantitative reverse-transcription polymerase chain reactions (qRT-PCR) were used to investigate the changes in miRNA expression due to the overexpression of PRL-3. Transwell chamber invasion assays, CCK-8 proliferation assays and RNA interference assays were used to explore the effects of PRL-3 on miR-21, miR-17 and miR-19a expression in colon cancer cells. Immunohistochemistry and qRT-PCR were performed in colon cancer tissues to evaluate the expression of PRL-3, signal transducer and activator of transcription 3 (STAT3), miR-21, miR-17 and miR-19a.

RESULTS

Our study demonstrated that the overexpression of PRL-3 in colon cancer cells induced the expression of miR-21, miR-17 and miR-19a by activating STAT3. Subsequently, these microRNAs contributed to the increased proliferation and invasiveness of the colon cancer cells. Positive correlations between PRL-3 and these microRNAs were also observed in matched primary colon cancer tissues and metastatic lesions.

CONCLUSION

miR-21, miR-17 and miR-19a induced by PRL-3 contribute to the proliferation and invasion of colon cancer.

摘要

背景

肝再生磷酸酶-3(PRL-3)是一种已知可促进肿瘤转移的癌基因,尤其是在结直肠癌(CRC)中。在这里,我们证明了 PRL-3 诱导的 miR-21、miR-17 和 miR-19a 的表达参与了结肠癌的增殖和转移。

方法

使用微阵列分析和定量逆转录聚合酶链反应(qRT-PCR)来研究由于 PRL-3 的过表达而导致的 miRNA 表达变化。Transwell 室侵袭实验、CCK-8 增殖实验和 RNA 干扰实验用于探索 PRL-3 对结肠癌细胞中 miR-21、miR-17 和 miR-19a 表达的影响。免疫组织化学和 qRT-PCR 用于评估结肠癌组织中 PRL-3、信号转导和转录激活因子 3(STAT3)、miR-21、miR-17 和 miR-19a 的表达。

结果

我们的研究表明,PRL-3 在结肠癌细胞中的过表达通过激活 STAT3 诱导 miR-21、miR-17 和 miR-19a 的表达。随后,这些 microRNAs 促进了结肠癌细胞的增殖和侵袭。在匹配的原发性结肠癌组织和转移性病变中,也观察到了 PRL-3 与这些 microRNAs 之间的正相关。

结论

PRL-3 诱导的 miR-21、miR-17 和 miR-19a 促进了结肠癌的增殖和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ca9/3394980/384b4d853020/bjc2012251f1.jpg

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