Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer.
Overexpression of miR-194 Reverses HMGA2-driven Signatures in Colorectal Cancer.
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DOI：
10.7150/thno.20041
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发表时间：
2017
期刊：
影响因子：
12.4
通讯作者：
Huang TC
中科院分区：
文献类型：
--
作者：
Chang HY;Ye SP;Pan SL;Kuo TT;Liu BC;Chen YL;Huang TC
结直肠癌（CRC）是全球癌症死亡的主要原因之一，在发达国家发病率和死亡率不断上升。癌基因和microrna调节CRC中的关键信号通路，并且已知是不受调控的。致癌转录调控因子高迁移率组AT-hook 2 （HMGA2）参与了包括CRC在内的多种癌症的转化，并与预后不良和远端转移密切相关。HMGA2及其共调控的miRs促进肿瘤进展的证据仍有待澄清。方法：我们对70例结直肠癌患者的表达谱进行了基因集富集分析，发现了包括miR-194在内的几种mir靶向的HMGA2相关基因。为了消除hmga2驱动的结直肠癌的致癌作用，我们重新表达miR-194，发现miR-194在体外和体内通过减少细胞增殖和肿瘤生长来发挥肿瘤抑制作用。结果：作为miR-194的直接上游抑制调节剂，HMGA2过表达降低了miR-194的表达和生物活性，而在高水平HMGA2细胞中重新表达miR-194会损害HMGA2的作用，影响细胞存活、上皮-间质转化过程和耐药性。结论：我们的研究结果表明，可以通过重新访问转录组图谱来发现新的分子相关性。我们发现miR-194与HMGA2一样重要，两者都以相反的行为协调调节结直肠癌的癌变，为高HMGA2表达的结直肠癌患者提供了替代的分子治疗方法。
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide with increasing incidence and mortality in developed countries. Oncogenes and microRNAs regulate key signaling pathways in CRC and are known to be deregulated. Oncogenic transcriptional regulator high-mobility group AT-hook 2 (HMGA2) participates in the transformation of several cancers including CRC and exhibits strong correlation with poor prognosis and distal metastasis. Evidence of HMGA2 and its co-regulated miRs contributing to tumor progression remains to be clarified. Methods: We performed gene-set enrichment analysis on the expression profiles of 70 CRC patients and revealed HMGA2 correlated genes that are targeted by several miRs including miR-194. To eliminate the oncogenic effects in HMGA2-driven CRC, we re-expressed miR-194 and found that miR-194 functions as a tumor suppressor by reducing cell proliferation and tumor growth in vitro and in vivo. Results: As a direct upstream inhibitory regulator of miR-194, overexpression of HMGA2 reduced miR-194 expression and biological activity, whereas re-expressing miR-194 in cells with high levels of HMGA2 impaired the effects of HMGA2, compromising cell survival, the epithelial-mesenchymal transition process, and drug resistance. Conclusion: Our findings demonstrate that novel molecular correlations can be discovered by revisiting transcriptome profiles. We uncover that miR-194 is as important as HMGA2, and both coordinately regulate the oncogenesis of CRC with inverted behaviors, revealing alternative molecular therapeutics for CRC patients with high HMGA2 expression.
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DOI：
10.1016/j.bbalip.2016.01.020
发表时间：
2016-08
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Eden ER
通讯作者：
Eden ER
DOI：
10.1083/jcb.200811005
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Rocha N;Kuijl C;van der Kant R;Janssen L;Houben D;Janssen H;Zwart W;Neefjes J
通讯作者：
Neefjes J
影响因子：
2.7
作者：
Chiang, Yeunpo;Song, Yongxi;Xu, Huimian
通讯作者：
Xu, Huimian
影响因子：
56.9
作者：
Mayr, Christine;Hemann, Michael T.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
4.3
作者：
Park, Sun-Mi;Shell, Scott;Peter, Marcus E.
通讯作者：
Peter, Marcus E.