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

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.

Aberrant expression of two miRNAs promotes proliferation, hepatitis B virus amplification, migration and invasion of hepatocellular carcinoma cells: evidence from bioinformatic analysis and experimental validation

“…In addition, the upregulation of miR-212-3p and miR-375 exerted opposite effects on TP53 expression, respectively suppressing and promoting its transcription. Recent studies have demonstrated that miR-221-3p functions as an oncogene in specific types of human cancer, including HCC (Wang et al, 2019), non-small cell lung cancer (Yin, Zhang & Li, 2019), glioma (Milani et al, 2019), gastric cancer and breast cancer (Deng et al, 2017). It was also reported that miR-375 inhibits the proliferation and migration of many cancer cells (Guo et al, 2018;Shen et al, 2014;Wu et al, 2017).…”

The pattern of gene copy number variations (CNVs) in hepatocellular carcinoma; in silico analysis

“…It has also been found that YY1AP1 interact with NeuroG3, SS18L2, ZMYM4, ZNF496 and ZNF576 -the proteins that apart from the rst two, altered expressions in HCC is reported in literatures [19][20][21]. Regarding the two microRNAs that target YY1AP1, hsa-miR-375 is a tumor suppressor [22] while hsa-miR-222-3p shows oncogenic properties [23]. The YY1AP1 is a component of the INO80 chromatin remodeling complex, which is responsible for transcriptional regulation, DNA repair, and replication [24].…”

Uncovering the Mechanism of the Effects of Pien-Tze-Huang on Liver Cancer Using Network Pharmacology and Molecular Docking

“…Verrier et al found that ESR1 is one of the key host factors of the liver virus and a target for the inhibition of the liver virus [ 32 ]. Wang et al also revealed that ESR1 is probably associated with HCC survival [ 33 ]. In this study, it was shown by target prediction and pathway enrichment that the bioactive compounds, glycolic acid hydrate, ginsenoside Rg1, and notoginsenoside R1, all act on the proteoglycans in cancer signal pathway and inhibit the progress of liver cancer by inhibiting the ESR1 transduction on the pathway.…”