High glucose regulates ERp29 in hepatocellular carcinoma by LncRNA MEG3-miRNA 483-3p pathway
High glucose regulates ERp29 in hepatocellular carcinoma by LncRNA MEG3-miRNA 483-3p pathway
复制标题
高糖通过LncRNA MEG3-miRNA 483-3p通路调节肝细胞癌中的ERp29
DOI：
10.1016/j.lfs.2019.116602
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发表时间：
2019-09-01
期刊：
影响因子：
6.1
通讯作者：
Yu, Pei
中科院分区：
文献类型：
--
作者：
Li, Xin;Cheng, Ting;Yu, Pei
目的：血糖失调是影响肝细胞癌（HCC）预后的一个不利因素。内质网（ER）被认为是癌症和糖尿病发展的关键组成部分。本研究旨在探讨肝癌合并糖尿病患者预后不良的机制，主要方法：采用蛋白质组学方法预测ER蛋白29（ERp 29）的表达，免疫组化、Western blot、CCK-8和细胞划痕试验检测高糖（HG）对肝癌细胞ERp 29表达的影响及生物学效应。生物信息学发现microRNA-483- 3 p之间存在竞争性内源RNA（ceRNA）调控网络（miR-483- 3 p）和长非编码RNA（LncRNA MEG 3）的表达、生物学效应以及HG对REp 29在肝癌细胞中的调节作用，进行双荧光素酶报告基因测定以研究ERp 29与miR-483- 3 p以及miR-483- 3 p与MEG 3的相互作用。HG上调HCC细胞中miR-483- 3 p的表达，miR-483- 3 p过表达抑制ERp 29的表达，并增加HCC细胞的增殖和迁移。此外，我们发现MEG 3在高糖培养基中孵育的HCC细胞中减少，并且MEG 3的敲低下调ERp 29表达。生物信息学分析发现，MEG 3通过与miR-483- 3 p结合发挥其保护作用。意义：本研究建立了LncRNA MEG 3/miR-483 - 3 p/ERp 29在肝癌中的调控网络，这可能有助于更好地理解高糖对肝癌预后不良的影响，并为糖尿病患者肝癌的诊断和治疗提供新的工具。
Aims: Blood glucose dysregulation is an adverse factor in the prognosis of hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) is thought to be crucial component in the development of cancer and diabetes. This study aimed to investigate the mechanisms of poor outcomes in HCC patients with diabetes.Main methods: ER protein 29 (ERp29) was predicted by proteomics, immunohistochemistry, Western blot, Cell Counting Kit-8 (CCK-8) and cell scratch test were used to identify the expression and biological effects of ERp29 under high glucose (HG) in HCC cells. Bioinformatics found a competing endogenous RNAs (ceRNAs) regulatory network between microRNA-483-3p (miR-483-3p) and Long noncoding RNA (LncRNA MEG3), the above methods also were used to identify their expression, biological effects and their roles of HG on regulation of REp29 in HCC cells, Dual-luciferase reporter assay was carried out to study the interaction of ERp29 with miR-483-3p and miR-483-3p with MEG3.Key findings: HG upregulated miR-483-3p expression in HCC cells and miR-483-3p overexpression suppressed ERp29 expression and also increased HCC cell proliferation and migration. Furthermore, we found that MEG3 was decreased in HCC cells incubated in medium with high glucose and knockdown of MEG3 downregulated ERp29 expression. Bioinformatics analysis found that MEG3 mediated its protective effects via binding to miR-483-3p.Significance: Overall, our study established a novel regulatory network of LncRNA MEG3/miR483-3p/ERp29 in HCC which may be helpful in better understanding the effect of high glucose on poor prognosis of HCC and in exploring new diagnostic and therapeutic tools for managing HCC in patients with diabetes.