Biostatistics mining associated method identifies AKR1B10 enhancing hepatocellular carcinoma cell growth and degenerated by miR-383-5p.
Biostatistics mining associated method identifies AKR1B10 enhancing hepatocellular carcinoma cell growth and degenerated by miR-383-5p.
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生物统计学挖掘相关方法鉴定出 AKR1B10 增强肝细胞癌细胞生长并通过 miR-383-5p 退化。
DOI：
10.1038/s41598-018-29271-3
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发表时间：
2018-07-23
影响因子：
4.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Wang J;Zhou Y;Fei X;Chen X;Chen Y
已有研究报道AKR 1B 10的异常表达与多种肿瘤的发生发展有关，但对AKR 1B 10在肝细胞癌（HCC）中的作用及其调控机制的研究还很有限。在这个项目中，我们通过GEO微阵列和TCGA RNAseq数据集的肿瘤/正常人体组织比较，鉴定了AKR 1B 10在HCC中作为癌基因的功能。对三种肝癌细胞系（SMMC-7721、HePG 2和HeP 3B）的进一步实验验证也表明AKR 1B 10在肝癌肿瘤生长中的个体发育功能。通过在HCC HeP 3B细胞中通过shRNA敲低AKR 1B 10，我们发现它显著诱导细胞周期停滞并抑制细胞生长。有趣的是，TCGA RNAseq数据和miRNA-seq数据的综合分析预测，miR-383- 5 p，一种新的转录后肿瘤抑制因子，与AKR 1B 10表达呈负相关。为了进一步研究miR-383- 5 p在HCC中调节AKR 1B 10的作用，我们进行了双荧光素酶报告基因测定实验。结果表明，miR-383- 5 p是转录后阶段靶向AKR 1B 10的上游调控因子。因此，我们报告了miR-383- 5 p调控的AKR 1B 10，促进了HCC肿瘤的进展，并可能成为HCC精准医学的潜在治疗靶点。
Previous studies have reported that the aberrantly expressed AKR1B10 is associated with many cancer development, however the functional roles of AKR1B10 and its regulatory mechanisms in hepatocellular carcinoma (HCC) have been limited studied. In this project, we identified AKR1B10 functional as an oncogene in HCC through tumor/normal human tissue comparison from both GEO microarray and TCGA RNAseq dataset. Further experimental validations from three HCC cell lines (SMMC-7721, HePG2 and HeP3B) also suggested the ontogenetic functions of AKR1B10 in HCC tumor growth. By knocking down AKR1B10 through shRNA in HCC HeP3B cells, we showed it significantly induced cell cycle arrest and inhibited cell growth. Interestingly, integrative analysis of TCGA RNAseq data and miRNA-seq data predicted that miR-383-5p, a novel post-transcriptional tumor suppressor, is negatively associated with AKR1B10 expression. To further investigate the role of miR-383-5p in regulating AKR1B10 in HCC, we performed Dual-luciferase reporter assay experiments. Results showed that miR-383-5p is an upstream modulator targeting AKR1B10 in the post-transcriptional stage. Thus, we report AKR1B10 modulated regulated by miR-383-5p, promotes HCC tumor progress, and could be potentially a therapeutic target for precision medicine in HCC.
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高表达Aldo-Keto还原酶1B10是肝细胞癌患者有利预后的独立预测指标。
影响因子：
3.4
作者：
Ha SY;Song DH;Lee JJ;Lee HW;Cho SY;Park CK
通讯作者：
Park CK
DOI：
10.1007/s10555-017-9712-y
发表时间：
2018-03
期刊：
Cancer metastasis reviews
影响因子：
--
作者：
Kim J;Yao F;Xiao Z;Sun Y;Ma L
通讯作者：
Ma L
DOI：
10.1073/pnas.1422749112
发表时间：
2015-08-25
影响因子：
11.1
作者：
Agerstam, Helena;Karlsson, Christine;Fioretos, Thoas
通讯作者：
Fioretos, Thoas
影响因子：
2.4
作者：
Azarbarzin, Shirin;Feizi, Mohammad Ali Hosseinpour;Fateh, Alavieh
通讯作者：
Fateh, Alavieh
影响因子：
3.3
作者：
Chen, X;Cheung, ST;Brown, PO
通讯作者：
Brown, PO