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靶向SIM2-s通过间充质-上皮转化减少胶质瘤细胞侵袭。

Targeting SIM2-s decreases glioma cell invasion through mesenchymal--epithelial transition.

作者信息

Su Yuhang, Wang Juntao, Zhang Xiaodan, Shen Jie, Deng Lin, Liu Qinglin, Li Gang

机构信息

Department of Emergency, Qi Lu Hospital, Shandong University, 250012, Jinan, China; Department of Neurosurgery, Qi Lu Hospital, Shandong University, 250012, Jinan, China.

出版信息

J Cell Biochem. 2014 Nov;115(11):1900-7. doi: 10.1002/jcb.24859.

Abstract

Glioma is a common primary intracranial carcinoma with high incidence, recurrence, and motility. Single minded homolog 2-short form (SIM2-s), a member of basic helix-loop-helix (bHLH) family, is reported to be expressed in glioma and might play a role in the invasion. In the present study, we investigated the importance of SIM2-s in glioma invasion and further explored the potential mechanisms. We showed that targeting SIM2-s by interference technology could decrease cell adhesion to fibronectin, induce cell aggregation and cytoskeletal changes. Furthermore, we showed that targeting SIM2-s increased the expression of epithelial markers and decreased the expression of mesenchymal markers, that is mesenchymal-epithelial transition (MET). Targeting SIM2-s decreased self-renewal of glioma stem cells by tumor sphere formation assay. Taken together, our results indicated that MET is involved in the inhibition of glioma invasion by targeting SIM2-s, and SIM2-s may be a new gene target.

摘要

胶质瘤是一种常见的原发性颅内癌,具有高发病率、高复发性和高迁移性。据报道,单 minded 同源物 2 短形式(SIM2-s)是碱性螺旋-环-螺旋(bHLH)家族的成员,在胶质瘤中表达,并可能在侵袭中发挥作用。在本研究中,我们研究了 SIM2-s 在胶质瘤侵袭中的重要性,并进一步探讨了潜在机制。我们发现,通过干扰技术靶向 SIM2-s 可降低细胞与纤连蛋白的粘附,诱导细胞聚集和细胞骨架变化。此外,我们发现靶向 SIM2-s 可增加上皮标志物的表达并降低间充质标志物的表达,即间充质-上皮转化(MET)。通过肿瘤球形成试验,靶向 SIM2-s 可降低胶质瘤干细胞的自我更新能力。综上所述,我们的结果表明,MET 通过靶向 SIM2-s 参与抑制胶质瘤侵袭,并且 SIM2-s 可能是一个新的基因靶点。

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