Dataset Information

In Silico and In Vivo Evaluation of microRNA-181c-5p's Role in Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is a fatal disease, accounting for 75-85% of primary liver cancers. The conclusive research on miR-181c-5p's role in hepatocarcinogenesis, whether it has oncogenic effects or acts as a tumor repressor, is limited and fluctuating. Therefore, the current study aimed to elucidate the role of miR-181c-5p in HCC in silico and in vivo. The bioinformatics analysis of miR-181c-5p expression data in HCC using several databases strongly shed light on its involvement in HCC development, but also confirmed the fluctuating data around its role. miR-181c-5p was proven here to have an oncogenic role by increasing HepG2 cells' viability as confirmed by MTT analysis. In addition, miR-181c-5p was upregulated in the HCC positive control group and progressed the HCC development and malignant features by its forced expression in an HCC mouse model by targeted delivery using a LA-PAMAM polyplex. This is indicated by the cancerous gross and histological features, and the significant increase in liver function biomarkers. The functional enrichment bioinformatics analyses of miR-181c-5p-downregulated targets in HCC indicated that miR-181c-5p targets were significantly enriched in multiple pathways and biological processes involved in HCC development. Fbxl3, an example for miR-181c-5p potential targets, downregulation and its correlation with miR-181c-5p were validated by qPCR. In conclusion, miR-181c-5p is upregulated in HCC and has an oncogenic role enhancing HCC progression.

SUBMITTER: Abd ElAziz ON

PROVIDER: S-EPMC9777864 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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In Silico and In Vivo Evaluation of microRNA-181c-5p's Role in Hepatocellular Carcinoma.

Abd ElAziz Omnia Nasser ON Elfiky Asmaa M AM Yassin Mohamed A MA Abd El-Hakam Fatma El-Zahraa FE Saleh Eman M EM El-Hefnawi Mahmoud M Mohamed Rania Hassan RH

Genes 20221212 12

Hepatocellular carcinoma (HCC) is a fatal disease, accounting for 75-85% of primary liver cancers. The conclusive research on miR-181c-5p's role in hepatocarcinogenesis, whether it has oncogenic effects or acts as a tumor repressor, is limited and fluctuating. Therefore, the current study aimed to elucidate the role of miR-181c-5p in HCC in silico and in vivo. The bioinformatics analysis of miR-181c-5p expression data in HCC using several databases strongly shed light on its involvement in HCC d ...[more]

PMID: 36553610

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Project description:O-GlcNAc Transferase (OGT) is a complementary enzyme that regulates O-linked N-acetylglucosaminylation(O-GlcNAcylation) and plays a critical role in various cancer phenotypes, including invasion, migration, and metabolic reprogramming. In our previous study we found that miR-7-5p was downregulated at lung cancer cells with highly metastatic capacity. In the in-silico approach, OGT is the predicted target of miR-7-5p. To identify miR-7-5p's role in cell growth and metabolism, we transfected various lung cancer cell lines with miR-7-5p. The expression level of miR-7-5p was confirmed by qRT-PCR in lung cancer cell lines. Western blot assays and qRT-PCR were performed to demonstrate miR-7-5p's effect. Bioinformatic analysis indicated that OGT is a direct target of miR-7-5p. The binding sites of miR-7-5p in the OGT 3' UTR were verified by luciferase reporter assay. To investigate the role of miR-7-5p in the cancer metabolism of non-small cell lung cancer (NSCLC) cells, mimic of miR-7-5p was transfected into NSCLC cells, and the effect of miR-7-5p on cancer metabolism was analyzed by LDH assays, glucose uptake, and mitochondrial ATP synthase inhibitor assay. O-GlcNAcylated protein level was determined by Western blot. The role of miR-7-5p in lung cancer growth was measured by MTS assays. To identify the delivery of miR-7-5p via PLGA, an in vitro release assay of PLGA-miR-7-5p was done. miR-7-5p was highly expressed whereas OGT showed low expression in H358, H827. However, miR-7-5p exhibited low expression while OGT had high expression in H522, H460, and H1299 cell lines. OGT were repressed by binding of miR-7a-5p to the 3'-UTR. Overexpression of miR-7-5p also diminished anaerobic glycolysis. miR-181a-5p transfection induced expression levels of OGT were diminished compared to those in the control group. O-GlcNAcylation was suppressed by miR-7-5p. Moreover, the overexpression of miR-7-5a suppressed lung cancer cell growth. miR-7-5p was released via PLGA for up to 10 days. In the present study, inhibition of OGT by miR-7-5p decreased the growth and cancer metabolism of lung cancer.

Dataset Information

In Silico and In Vivo Evaluation of microRNA-181c-5p's Role in Hepatocellular Carcinoma.

Publications

In Silico and In Vivo Evaluation of microRNA-181c-5p's Role in Hepatocellular Carcinoma.

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