生物信息学和实验洞察 miR-182、hsa_circ_0070269 和 circ-102,166 作为 HCV 相关 HCC 的治疗靶点。

Bioinformatics and Experimental Insights Into miR-182, hsa_circ_0070269, and circ-102,166 as Therapeutic Targets for HCV-Associated HCC.

机构信息

Institute of Molecular Biology and Biotechnology (IMBB), University of Lahore (UOL), Lahore, Pakistan.

Department of Biomedical Engineering, UET Lahore, Narowal, Pakistan.

出版信息

Cancer Rep (Hoboken). 2024 Dec;7(12):e70049. doi: 10.1002/cnr2.70049.

DOI:10.1002/cnr2.70049

PMID:39617640

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11608829/

Abstract

AIMS

Hepatocellular carcinoma (HCC) is a type of malignant tumor and the sixth leading cause of death worldwide. It is caused by HBV, HCV infection, and alcohol consumption. MicroRNAs are typically small, non-coding RNAs that are involved in the regulation of mRNA expression. Recent studies revealed miRNAs' regulatory roles in liver cancer, linked to risk factors like HCV, HBV infection, alcoholism, drug use, and auto-immune hepatic disorders. Circular RNAs also belong to the class of non-coding RNAs; they act as ceRNAs to regulate miRNA expression and regulate different oncogenic pathways in HCC progression. This study aimed to check the hsa_circ_0070269, circ-102,166 (hsa_circ_0004913), and miR-182 expression in HCV induced HCC patients.

METHODS

Data analysis was used to find out studies related to the role of hsa_circ_0070269, circ-102,166, and miR-182 in HCC; miR-182 targeted genes, their role in different diseases; and miR-182 interactions with hsa_circ_0070269 and circ-102,166 in the HCC. It was revealed that the hsa_circ_0070269, circ-102,166, and miR-182 correlations in HCV induced HCC have not been explored yet. Therefore, to validate data from literature mining, expression analysis of dysregulated hsa_circ_0070269, circ-102,166, and miR-182 was performed in HCV induced HCC patients using RT-PCR.

RESULTS

It was found that miR-182 was significantly upregulated and acts as an oncomiRNA in HCV induced HCC, and hsa_circ_0070269 and circ-102,166 were downregulated in HCV induced HCC. We have identified that miR-182 relative expression level was significantly high (p < 0.0029), while has_circ_0070269 (p < 0.002) and circ-102,166 (p < 0.002) were significantly downregulated in HCV-HCC patients as compared to expression in healthy individuals.

CONCLUSION

Our data revealed that miR-182 acts as an oncomiRNA in HCC development. Hsa_circ_0070269 and circ-102,166 are highly expressed in healthy controls compared to HCV induced HCC patients, can sponge miR-182 expression by acting as tumor suppressors, and can be used as biomarkers and targets for HCC treatment.

摘要

目的

肝细胞癌（HCC）是一种恶性肿瘤，也是全球第六大致死原因。它由 HBV、HCV 感染和酒精摄入引起。微小 RNA 通常是参与调节 mRNA 表达的小型非编码 RNA。最近的研究表明，miRNA 在肝癌中的调控作用与 HCV、HBV 感染、酒精中毒、药物使用和自身免疫性肝紊乱等风险因素有关。环状 RNA 也属于非编码 RNA 类；它们作为 ceRNA 调节 miRNA 的表达，并调节 HCC 进展中不同的致癌途径。本研究旨在检查 HCV 诱导的 HCC 患者中 hsa_circ_0070269、circ-102,166（hsa_circ_0004913）和 miR-182 的表达。

方法

数据分析用于寻找与 hsa_circ_0070269、circ-102,166 和 miR-182 在 HCC 中的作用相关的研究；miR-182 的靶基因及其在不同疾病中的作用；以及 miR-182 与 hsa_circ_0070269 和 circ-102,166 在 HCC 中的相互作用。结果表明，hsa_circ_0070269、circ-102,166 和 miR-182 在 HCV 诱导的 HCC 中的相关性尚未得到探索。因此，为了验证文献挖掘数据，使用 RT-PCR 对 HCV 诱导的 HCC 患者中失调的 hsa_circ_0070269、circ-102,166 和 miR-182 的表达进行了分析。

结果

发现 miR-182 在 HCV 诱导的 HCC 中显著上调并作为致癌 miRNA 发挥作用，而 hsa_circ_0070269 和 circ-102,166 在 HCV 诱导的 HCC 中下调。我们已经确定，miR-182 的相对表达水平显著升高（p<0.0029），而 hsa_circ_0070269（p<0.002）和 circ-102,166（p<0.002）在 HCV-HCC 患者中的表达明显低于健康个体。

结论

我们的数据表明，miR-182 在 HCC 发展中起致癌 miRNA 的作用。与 HCV 诱导的 HCC 患者相比，hsa_circ_0070269 和 circ-102,166 在健康对照中高表达，可通过作为肿瘤抑制因子来海绵吸附 miR-182 的表达，并可作为 HCC 治疗的生物标志物和靶点。