An in silico integrative analysis of hepatocellular carcinoma omics databases shows the dual regulatory role of microRNAs either as tumor suppressors or as oncomirs

Mahmoud M. Tolba, Bangli Soliman,Abdul Jabbar,HebaT’Allah Nasser, Mahmoud Elhefnaw

medRxiv (Cold Spring Harbor Laboratory)(2021)

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Abstract
MicroRNAs are well known as short RNAs bases, 22 nucleotides, binding directly to 3’untranslated region (3’UTR) of the messenger RNA to repress their functions. Recently, microRNAs have been widely used as a therapeutic approach for various types of Cancer. MicroRNA is categorized into tumor suppressor and oncomirs. Tumor suppressor microRNAs can repress the pathologically causative oncogenes of the hallmarks of Cancer. However, based on the fact that miRNA has no proper fidelity to bind specific mRNAs due to binding to off-targets, it results in a kind of inverse biological activity. Here, we have executed an in-silico integrative analysis of GEO/TCGA-LIHC of genes/microRNAs expression analysis in HCC, including (446 HCC vs. 146 normal specimens for miRNAs expression) ad 488 specimens for genes expression. It virtually shows that microRNAs could have an ability to target both oncogenes and tumor suppressor genes that contribute to its dual activity role as a tumor suppressor and oncomirs via miRNA-lncRNA-TFs-PPI Crosstalk. Seven resultant microRNAs show a putative dual role in HCC. It enhances our concluded suggestion of using combination therapy of tumor suppressor genes activators with microRNAs. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We have no external fund. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All the data is available by requesting from the corresponding author.
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Key words
hepatocellular carcinoma omics databases,hepatocellular carcinoma,micrornas,tumor suppressors
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