miR-144-3p exerts anti-tumor effects in glioblastoma by targeting c-Met
miR-144-3p exerts anti-tumor effects in glioblastoma by targeting c-Met
复制标题
DOI：
10.1111/jnc.13272
复制
发表时间：
2015-10-01
影响因子：
4.7
通讯作者：
Yue, Xiao
中科院分区：
文献类型：
--
作者：
Lan, Fengming;Yu, Huiming;Yue, Xiao
本研究旨在探讨miR-144- 3 p在不同磷酸酶和张力蛋白同源物（phosphatase and tensin homolog，PTEN）表型胶质母细胞瘤（glioblastoma，GBM）细胞中的特异性功能和作用机制。我们发现miR-144- 3 p在胶质瘤组织中的表达水平较非肿瘤性脑组织明显下调，且随着级别的升高而降低。miR-144- 3 p的缺失有效预测了胶质瘤患者总体生存率的降低。有趣的是，MET在胶质瘤组织中的表达上调，并且与miR-144- 3 p水平呈负相关。接下来，我们证明miR-144- 3 p特异性结合MET 3-非翻译区（3 UTR）并抑制其表达。miR-144- 3 p通过体外和体内抑制MET而有效地抑制GBM细胞增殖和侵袭。此外，我们的结果显示，在具有不同PTEN表型的GBM细胞中，miR-144- 3 p诱导的恶性肿瘤抑制没有差异。miR-144- 3 p通过靶向MET抑制GBM细胞中的几种存活信号通路，而不依赖于PTEN状态。miR-144- 3 p的过表达抑制了存活能力并增加了凋亡，导致放射和替莫唑胺敏感性的增强。我们的研究结果为miR-144- 3 p通过靶向MET并抑制下游信号通路在GBM治疗中的潜在应用提供了新的见解。
The study aimed to explore the specific function and mechanism of miR-144-3p in glioblastoma (GBM) cells with different phosphatase and tensin homolog (PTEN) phenotypes. We demonstrated that the miR-144-3p level was significantly down-regulated in glioma compared with the non-neoplastic brain tissues, and decreased with ascending grades. The loss of miR-144-3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up-regulated and inversely associated with miR-144-3p level in glioma tissues. Next, we certified that miR-144-3p specifically bound to MET 3-untranslated region (3 UTR) and inhibited its expression. miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing METinvitro and invivo. In addition, our results showed no difference in malignancy inhibition induced by miR-144-3p in GBM cells with different PTEN phenotypes. miR-144-3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Over-expression of miR-144-3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide sensitivity. Our data provide new insights into the potential application of miR-144-3p in GBM therapy bytargeting MET and then inhibiting the downstream signaling.