MiR-26a regulates cell cycle and anoikis of human esophageal adenocarcinoma cells through Rb1-E2F1 signaling pathway

MiR-26a regulates cell cycle and anoikis of human esophageal adenocarcinoma cells through Rb1-E2F1 signaling pathway
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MiR-26a通过Rb1-E2F1信号通路调控人食管腺癌细胞的细胞周期和失巢凋亡

DOI:
10.1007/s11033-012-2222-7
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发表时间:
2012-10
影响因子:
2.8
通讯作者:
Wang, Rong-Quan
Wang, Rong-Quan
中科院分区:
生物学4区
文献类型:
--
作者:
Fang, Dian-Chun;Zhang, An-Ran;Zhang, Bi-Cheng;Rao, Zhi-Guo;Gao, Jian-Fei;Lv, Mu-Han;Wu, Yu-Yun;Wang, Su-Min;Wang, Rong-Quan

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对anoikis的抵抗是一种由缺乏基质粘附诱导的细胞凋亡亚型,有助于恶性转化和转移的发展。microrna在肿瘤发生和转移中起着关键的调节作用。在本研究中,我们描述了在肿瘤细胞中通常下调的miR-26a参与了人食管腺癌(EA)细胞嗜酒耐药的获得。临床样本的qRT-PCR结果显示miR-26a表达下调与EA的肿瘤发生和转移有关,体外实验确定miR-26a直接参与人EA OE33细胞的细胞周期和细胞形态的调控。此外,我们发现Rb1是miR-26a的直接功能靶点,并揭示miR-26a表达的降低导致Rb1蛋白水平升高,从而抑制E2F1的功能,从而影响细胞周期和anoikis的表型。我们在这里报道的研究结果提供了miR-26a可能参与EA细胞抗气味的调节的证据。靶向miR-26a可能提供一种抑制转移的新策略。
Resistance to anoikis, the subtype of apoptosis induced by lack of matrix adhesion, contributes to malignant transformation and development of metastasis. MicroRNAs play key regulatory roles in tumorigenesis and metastasis. In this study, we described that miR-26a, which is usually downregulated in tumor cells, is involved in the acquisition of anoikis-resistance of human esophageal adenocarcinoma (EA) cells. Results of qRT-PCR in clinical samples showed that downregulated miR-26a expression is related to tumorigenesis and metastasis of EA. In vitro experiments determined that miR-26a directly participates in the regulation of cell cycle and anoikis of human EA OE33 cells. Further, we identified that Rb1 is the direct functional target of miR-26a, and revealed that the reduction of miR-26a expression leads to increased Rb1 protein level and thus inhibits the function of E2F1, by which it influences the phenotypes of cell cycle and anoikis. The findings we reported here presented the evidence that miR-26a may be involved in regulation of anoikis-resistance of EA cells. Targeting miR-26a may provide a novel strategy to inhibit metastasis.
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