MiR-467a is upregulated in radiation-induced mouse thymic lymphomas and regulates apoptosis by targeting Fas and Bax.
MiR-467a is upregulated in radiation-induced mouse thymic lymphomas and regulates apoptosis by targeting Fas and Bax.
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MiR-467a 在辐射诱导的小鼠胸腺淋巴瘤中表达上调，并通过靶向 Fas 和 Bax 调节细胞凋亡。
DOI：
10.7150/ijbs.10276
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发表时间：
2015
影响因子：
9.2
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Gao F;Chen S;Sun M;Mitchel RE;Li B;Chu Z;Cai J;Liu C
已经报道了某些microRNA（miRNAs / miRs）的失调参与肿瘤发生。然而，与放射致癌相关的miRNAs仍不明确。在这项研究中，我们验证了miR-467 a在辐射诱导的小鼠胸腺淋巴瘤组织中的上调。然后，我们研究了miR-467 a是否在胸腺淋巴瘤细胞中作为致癌miRNA发挥作用。为此，我们评估了miR-467 a对胸腺淋巴瘤细胞的生物学效应。利用miRNA微阵列，我们发现四种miRNA（miR-467 a，miR-762，miR-455和miR-714）是肿瘤组织中上调最多（>4倍）的miRNA。生物信息学预测miR-467 a可能通过靶向Fas和Bax调控细胞凋亡途径。结果表明，转染miR-467 a的细胞增殖能力和集落形成能力均显著增强，凋亡率降低;而敲低miR-467 a的细胞增殖能力受到抑制，凋亡率增加，提示miR-467 a可能参与了细胞凋亡的调控。此外，在体内肿瘤移植模型中，miR-467 a敲低导致更小的肿瘤和更好的预后。为了解释miR-467 a抑制细胞凋亡的机制，我们使用流式细胞术和免疫印迹法研究了候选靶基因（Fas和Bax）在miR-467 a转染的细胞中相对于阴性对照转染的细胞的表达。Fas和Bax在miR-467 a转染的EL 4和NIH 3 T3细胞中普遍下调，并且所有基因在其mRNA的3 'UTR中都含有miR-467 a靶序列。Fas和Bax在辐射诱导的胸腺淋巴瘤组织中实际上下调，因此两者都被鉴定为胸腺淋巴瘤中miR-467 a的可能靶点。为了确定Fas和/或Bax的下调是否参与miR-467 a的凋亡抑制，我们将表达Fas和Bax的载体转染到miR-467 a上调的EL 4细胞中。我们发现Fas和Bax的过表达均降低了细胞的存活率，同时增加了凋亡率，这表明Fas和Bax的下调可能至少部分地负责miR-467 a对凋亡的抑制。这些数据表明，miR-467 a可能在辐射诱导的胸腺淋巴瘤细胞中具有致癌功能，并且其表达增加可能通过Fas和Bax的异常表达赋予肿瘤细胞生长优势。
It has been reported dysregulation of certain microRNAs (miRNAs / miRs) is involved in tumorigenesis. However, the miRNAs associated with radiocarcinogenesis remain undefined. In this study, we validated the upregulation of miR-467a in radiation-induced mouse thymic lymphoma tissues. Then, we investigated whether miR-467a functions as an oncogenic miRNA in thymic lymphoma cells. For this purpose, we assessed the biological effect of miR-467a on thymic lymphoma cells. Using miRNA microarray, we found four miRNAs (miR-467a, miR-762, miR-455 and miR-714) were among the most upregulated (>4-fold) miRNAs in tumor tissues. Bioinformatics prediction suggests miR-467a may potentially regulate apoptosis pathway via targeting Fas and Bax. Consistently, in miR-467a-transfected cells, both proliferation and colony formation ability were significantly increased with decrease of apoptosis rate, while, in miR-467a-knockdown cells, proliferation was suppressed with increase of apoptosis rate, indicating that miR-467a may be involved in the regulation of apoptosis. Furthermore, miR-467a-knockdown resulted in smaller tumors and better prognosis in an in vivo tumor-transplanted model. To explain the mechanism of apoptosis suppression by miR-467a, we explore the expression of candidate target genes (Fas and Bax) in miR-467a-transfected relative to negative control transfected cells using flow cytometry and immunoblotting. Fas and Bax were commonly downregulated in miR-467a-transfected EL4 and NIH3T3 cells, and all of the genes harbored miR-467a target sequences in the 3'UTR of their mRNA. Fas and Bax were actually downregulated in radiation-induced thymic lymphoma tissues, and therefore both were identified as possible targets of miR-467a in thymic lymphoma. To ascertain whether downregulation of Fas and / or Bax is involved in apoptosis suppression by miR-467a, we transfected vectors expressing Fas and Bax into miR-467a-upregulated EL4 cells. Then we found that both Fas- and Bax-overexpression decreased cell viability with increase of apoptosis rate, indicating that downregulation of Fas and Bax may be at least partly responsible for apoptosis suppression by miR-467a. These data suggest that miR-467a may have oncogenic functions in radiation-induced thymic lymphoma cells and that its increased expression may confer a growth advantage on tumor cells via aberrant expression of Fas and Bax.
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影响因子：
8
作者：
Huang, L;Snyder, AR;Morgan, WF
通讯作者：
Morgan, WF
影响因子：
56.9
作者：
Mayr, Christine;Hemann, Michael T.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1042/bj20101585
发表时间：
2011-03-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Patel N;Tahara SM;Malik P;Kalra VK
通讯作者：
Kalra VK
影响因子：
64.5
作者：
Marson A;Levine SS;Cole MF;Frampton GM;Brambrink T;Johnstone S;Guenther MG;Johnston WK;Wernig M;Newman J;Calabrese JM;Dennis LM;Volkert TL;Gupta S;Love J;Hannett N;Sharp PA;Bartel DP;Jaenisch R;Young RA
通讯作者：
Young RA
伽马射线照射通过下调 CCR7 和诱导细胞凋亡来损害树突状细胞向 CCL19 的迁移
影响因子：
9.2
作者：
Liu C;Lin J;Zhao L;Yang Y;Gao F;Li B;Cui J;Cai J
通讯作者：
Cai J