Suppr超能文献

从计算角度看 MEG3/miR664a-3p/ADH4 轴的新见解及其在肝细胞癌中的可能作用。

Novel Insights into MEG3/miR664a-3p/ADH4 Axis and Its Possible Role in Hepatocellular Carcinoma from an in Silico Perspective.

机构信息

Department of Biochemistry, Center of Excellence in Molecular Biology & Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, India.

出版信息

Genes (Basel). 2022 Nov 30;13(12):2254. doi: 10.3390/genes13122254.

Abstract

Hepatocellular carcinoma (HCC) is a complex disease involving altered interactomes of transcripts and proteins. MicroRNAs (miRNAs) are small-noncoding RNAs that can interact with specific gene transcripts and an array of other vital endogenous non-coding RNAs (lncRNAs) that can influence gene expression. Maternally Expressed Gene 3 (MEG3) is an imprinted lncRNA that is reported to be downregulated in HCC (in both cell lines and tumors). Alcohol Dehydrogenase 4 (ADH4) is a well-known prognostic protein biomarker for predicting the survival outcomes of patients with hepatocellular carcinoma whose expression is regulated by miR-664a-3p, which is upregulated in HCC. In this study, we performed a battery of robust and systematic in silico analyses to predicate the possible lncRNA-miRNA interactions between MEG3, miR-664a-3p, and ADH4. miRNA-mRNA and lncRNA-miRNA hybrid structures were primarily obtained, and the minimum free energies (MFEs) for the 3'UTR (Untranslated Regions) of ADH4-miR-664a-3p and the 3'UTR of MEG3-miR-664a-3p interactions were assessed to predict the stability of the obtained RNA heteroduplex hybrids. The hybrid with the least minimum free energy (MFE) was considered to be the most favorable. The MFEs were around -28.1 kcal/mol and -31.3 kCal/mol for the ADH4-miR-664a-3p and MEG3-miR-66a-3p RNA hybrids, respectively. This demonstrated that lncRNA-MEG3 might be a competitive endogenous RNA that acts as a molecular sponge for miR-664a-3p. In summary, our interaction analyses results predict the significance of the MEG3/miR-664a-3p/ADH4 axis, where MEG3 downregulation results in miR-664a-3p overexpression and the subsequential underexpression of ADH4 in HCC, as a novel axis of interest that demands further validation.

摘要

肝细胞癌(HCC)是一种涉及转录本和蛋白质相互作用改变的复杂疾病。微小 RNA(miRNA)是一种小的非编码 RNA,可以与特定的基因转录本相互作用,还可以与一系列其他重要的内源性非编码 RNA(lncRNA)相互作用,从而影响基因表达。母系表达基因 3(MEG3)是一种印迹的 lncRNA,据报道在 HCC(细胞系和肿瘤中)中下调。醇脱氢酶 4(ADH4)是一种众所周知的预测肝细胞癌患者生存结果的预后蛋白生物标志物,其表达受 miR-664a-3p 调控,而 miR-664a-3p 在 HCC 中上调。在这项研究中,我们进行了一系列强大而系统的计算分析,以预测 MEG3、miR-664a-3p 和 ADH4 之间可能的 lncRNA-miRNA 相互作用。首先获得了 miRNA-mRNA 和 lncRNA-miRNA 杂交结构,并评估了 ADH4-miR-664a-3p 的 3'UTR(非翻译区)和 MEG3-miR-664a-3p 相互作用的 3'UTR 的最小自由能(MFEs),以预测获得的 RNA 杂合体的稳定性。具有最小最小自由能(MFE)的杂交体被认为是最有利的。ADH4-miR-664a-3p 和 MEG3-miR-66a-3p RNA 杂合体的 MFE 分别约为-28.1 kcal/mol 和-31.3 kCal/mol。这表明 lncRNA-MEG3 可能是一种竞争性内源 RNA,作为 miR-664a-3p 的分子海绵。总之,我们的相互作用分析结果预测了 MEG3/miR-664a-3p/ADH4 轴的重要性,其中 MEG3 的下调导致 miR-664a-3p 的过表达,继而导致 HCC 中 ADH4 的表达下调,作为一个新的值得关注的轴,需要进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04d6/9778073/988fcbdb1ba7/genes-13-02254-g001.jpg

相似文献

3
High glucose regulates ERp29 in hepatocellular carcinoma by LncRNA MEG3-miRNA 483-3p pathway.
Life Sci. 2019 Sep 1;232:116602. doi: 10.1016/j.lfs.2019.116602. Epub 2019 Jun 26.
5
Inhibition of miR-664a interferes with the migration of osteosarcoma cells via modulation of MEG3.
Biochem Biophys Res Commun. 2017 Aug 26;490(3):1100-1105. doi: 10.1016/j.bbrc.2017.06.174. Epub 2017 Jun 29.
6
lncRNA MEG3 inhibits the growth of hepatocellular carcinoma cells by sponging miR-9-5p to upregulate SOX11.
Braz J Med Biol Res. 2019;52(10):e8631. doi: 10.1590/1414-431X20198631. Epub 2019 Sep 16.
7
microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer.
Oncogene. 2011 Nov 24;30(47):4750-6. doi: 10.1038/onc.2011.193. Epub 2011 May 30.
10
Overexpression Of hsa-miR-664a-3p Is Associated With Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Via Targeting FHL1.
Int J Chron Obstruct Pulmon Dis. 2019 Oct 9;14:2319-2329. doi: 10.2147/COPD.S224763. eCollection 2019.

本文引用的文献

2
A novel four-gene signature for predicting the prognosis of hepatocellular carcinoma.
Scand J Gastroenterol. 2022 Oct;57(10):1227-1237. doi: 10.1080/00365521.2022.2069476. Epub 2022 May 5.
3
The emerging role of lncRNA MEG3 and MEG3 rs7158663 in hepatocellular carcinoma.
Eur Rev Med Pharmacol Sci. 2022 Jan;26(1):11-21. doi: 10.26355/eurrev_202201_27742.
5
Molecular Signature and Immune Landscape of HCV-Associated Hepatocellular Carcinoma (HCC): Differences and Similarities with HBV-HCC.
J Hepatocell Carcinoma. 2021 Nov 21;8:1399-1413. doi: 10.2147/JHC.S325959. eCollection 2021.
6
Current epidemiology in hepatocellular carcinoma.
Expert Rev Gastroenterol Hepatol. 2021 Nov;15(11):1295-1307. doi: 10.1080/17474124.2021.1991792. Epub 2021 Oct 22.
7
NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options.
J Hepatol. 2022 Feb;76(2):446-457. doi: 10.1016/j.jhep.2021.09.007. Epub 2021 Sep 20.
8
Epidemiology and risk-stratification of NAFLD-associated HCC.
J Hepatol. 2021 Dec;75(6):1476-1484. doi: 10.1016/j.jhep.2021.08.012. Epub 2021 Aug 25.
9
Prognostic Value of and Its Correlation With Immune Infiltrates in Gliomas.
Front Genet. 2021 Jun 16;12:679097. doi: 10.3389/fgene.2021.679097. eCollection 2021.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验