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

生物信息学和实验研究揭示 miR-182、hsa_circ_0070269 和 circ-102,166 作为 HCV 相关 HCC 的治疗靶点

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作者:Ishaq Yasmeen, Rauff Bisma, Alzahrani Badr, Ikram Aqsa, Javed Hasnain, Abdullah Imran, Mujtaba Ghulam
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.

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