The low expression of miR-451 predicts a worse prognosis in non-small cell lung cancer cases.
The low expression of miR-451 predicts a worse prognosis in non-small cell lung cancer cases.
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DOI：
10.1371/journal.pone.0181270
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Maeda D
中科院分区：
文献类型：
--
作者：
Goto A;Tanaka M;Yoshida M;Umakoshi M;Nanjo H;Shiraishi K;Saito M;Kohno T;Kuriyama S;Konno H;Imai K;Saito H;Minamiya Y;Maeda D
miR-451是一种具有肿瘤抑制作用的microRNA，具有多个靶基因，包括巨噬细胞迁移抑制因子（MIF）。由于对mir-451在NSCLC中的表达及其临床病理意义知之甚少，我们对370例NSCLC进行了临床病理学研究，以明确其表达。还对NSCLC细胞系进行了细胞生物学实验，以确认miR-451的肿瘤抑制作用以及miR-451是否靶向MIF。我们采用实时定量聚合酶链反应和免疫组化方法分别检测了370例NSCLC组织中miR-451和MIF的表达。还评估了84份背景肺组织样本的miR-451表达。研究的临床病理和遗传因素包括无病生存期、吸烟状况、组织学类型、疾病分期、EGFR基因突变和ALK重排。在286例腺癌病例中，还评估了浸润状态（原位腺癌、微创腺癌和浸润腺癌）。培养5种NSCLC细胞系（H23、H441、H522、H1703和H1975）并评价其miR-451和MIF表达。选择miR-451低表达和MIF高表达的细胞株，转染miR-451模拟物，观察其对MIF表达、Akt和Erk状态、细胞增殖和细胞迁移的影响。miR-451在肺癌组织中的表达明显低于背景肺组织（P <0.0001）。疾病晚期、胸膜浸润阳性、淋巴结状态和吸烟者等因素与miR-451的低表达显著相关（均P <0.05），而EGFR基因突变和ALK重排与此无关。腺癌中浸润性和微浸润性腺癌的miR-451表达低于原位腺癌（P <0.0005）。生存分析显示，miR-451的低表达是NSCLC预后不良的独立预测因子（P <0.05）。MIF表达与miR-451表达呈负相关。在检测的5种NSCLC细胞系中，H441和H1975显示出较高的MIF和较低的miR-451表达。转染miR-451模拟物后，这些细胞系的MIF表达和磷酸化Akt表达受到抑制，细胞增殖和细胞迁移也受到抑制。这项对370例NSCLC病例的临床病理学研究和NSCLC细胞系的细胞生物学研究阐明了miR-451的肿瘤抑制作用及其预后价值。我们还验证了MIF作为NSCLC中miR-451的靶点。
miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migration inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451. We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration. The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration. This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC.
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影响因子：
7.5
作者：
Liu, Wei;Liu, Sheng-Yao;Yu, Bin
通讯作者：
Yu, Bin
影响因子：
20.4
作者：
von der Thusen, Jan H.;Tham, Yuen S.;Nicholson, Andrew G.
通讯作者：
Nicholson, Andrew G.
Notch-1 通过 AP-1/microRNA-451 介导的 MDR-1 调节赋予肺腺癌对紫杉烷类化学耐药性
DOI：
10.1038/mtna.2016.82
发表时间：
2016-10-11
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
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影响因子：
8.4
作者：
Chen, Dongqin;Huang, Jiayuan;Chen, Longbang
通讯作者：
Chen, Longbang
影响因子：
5.6
作者：
Warth, Arne;Muley, Thomas;Weichert, Wilko
通讯作者：
Weichert, Wilko