Department of Biochemistry, Center of Excellence in Molecular Biology & Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, India.
Genes (Basel). 2022 Nov 30;13(12):2254. doi: 10.3390/genes13122254.
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.
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。