J Cancer 2019; 10(11):2520-2533. doi:10.7150/jca.29207

Research Paper

Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma

Xiangkun Wang1, Xiwen Liao1, Ketuan Huang1, Xianmin Zeng1, Zhengqian Liu1, Xin Zhou1, Tingdong Yu1, Chengkun Yang1, Long Yu1,2, Qiaoqi Wang3, Chuangye Han1, Guangzhi Zhu1, Xinping Ye1, Tao Peng1✉

1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China;
2. Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan Province, China;
3. Department of Medical Cosmetology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530000, Guangxi Province, China

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Citation:
Wang X, Liao X, Huang K, Zeng X, Liu Z, Zhou X, Yu T, Yang C, Yu L, Wang Q, Han C, Zhu G, Ye X, Peng T. Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma. J Cancer 2019; 10(11):2520-2533. doi:10.7150/jca.29207. Available from http://www.jcancer.org/v10p2520.htm

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Abstract

Objective: MicroRNAs (miRNAs) have been explored in malignancies. We investigated the functions of clustered miRNAs hsa-miR-221/222-3p in hepatocellular carcinoma (HCC).

Methods: Human miRNA tissue atlas website was determined expression levels in liver tissue. Four databases, TarBase, miRTarBase, miRecords and miRPathDB, were found experimentally validated target genes of clustered miRNAs. TargetScanHuman was predicted target genes. The STRING website was depicted protein-protein interaction (PPI) networks. The OncoLnc website analyzed prognostic values for hsa-miR-221/222-3p and their target genes. The MCODE plugin calculated modules of PPI networks. Receiver operating characteristic (ROC) curves were predicted 1, 3, and 5 years prognostic values.

Results: Expression of clustered miRNAs was high in liver tissues. A total of 1577 target genes were identified. Enrichment analysis showed that target genes were enriched mainly in cancer, Wnt signaling and ErbB signaling pathways. Two modules were calculated using PPI networks. Has-miR-221-3p was not associated with prognosis (P = 0.401). Has-miR-222-3p and target genes ESR1, TMED7, CBFB, ETS2, UBE2J1 and UBE2N of the clustered miRNAs were associated with HCC survival (all P < 0.05). Has-miR-222-3p, CBFB, and UBE2N showed good performance of ROC in prognosis prediction at 1, 3, and 5 years (all area under curves > 0.600).

Conclusion: Has-miR-222-3p and target genes, especially CBFB, UBE2N, may serve as prognostic predictors for HCC.

Keywords: microRNA, hsa-miR-221-3p, hsa-miR-222-3p, gene, hepatocellular carcinoma, prognosis