Construction of AP003469.4-miRNAs-mRNAs ceRNA network to reveal potential biomarkers for hepatocellular carcinoma

Tengyang Fan; Guojun Jiang; Rongshu Shi; Ronghua Yu; Xue Xiao; Di Ke

Construction of AP003469.4-miRNAs-mRNAs ceRNA network to reveal potential biomarkers for hepatocellular carcinoma

Am J Cancer Res. 2022 Apr 15;12(4):1484-1501. eCollection 2022.

Authors

Tengyang Fan¹, Guojun Jiang², Rongshu Shi², Ronghua Yu³, Xue Xiao¹, Di Ke^{1

2}

Affiliations

¹ Department of General Medicine, Affiliated Hospital of Zunyi Medical University 149 Dalian Road, Huichuan District, Zunyi 563003, Guizhou, China.
² Department of Intervention, Affiliated Hospital of Zunyi Medical University 149 Dalian Road, Huichuan District, Zunyi 563003, Guizhou, China.
³ Department of Nuclear Medicine, Affiliated Hospital of Zunyi Medical University 149 Dalian Road, Huichuan District, Zunyi 563003, Guizhou, China.

PMID: 35530270
PMCID: PMC9077056

Abstract

Studies have reported that the competing endogenous RNA (ceRNA) networks are related to disease progression and prognosis in patients with hepatocellular carcinoma (HCC). The roles and mechanisms of long-chain non-coding RNA AP003469.4 in HCC have remained unclear. Here, we explored the roles of AP003469.4 in HCC progression using bioinformatics, CCK-8, Transwell assay, etc. AP003469.4 targets miRNAs and these target genes were predicted by the LncBase Predicted v.2, miRDB, miRTarBase, and TargetScan databases. Then, AP003469.4-associated ceRNA network was constructed. Biological functions and mechanisms of differentially expressed genes in the ceRNA network were explored using GO and KEGG. Survival analysis and Cox regression analysis were used to screen prognostic genes and construct a prognostic risk model. The results revealed that AP003469.4, with the area under the curve of 0.9048, was highly expressed in HCC tissues. Increased expression of AP003469.4 was an independent risk factor for the dismal prognosis of HCC patients and was associated with the short overall and disease-free survival. Downregulation of AP003469.4 expression inhibited cell proliferation, cycle transition, invasion, and migration, and promoted cell apoptosis. There were 489 differentially expressed target genes in the ceRNA network, which were involved in several pathways, such as the MAPK signaling pathway, cell cycle, and p53 signaling pathway. The risk model was based on the DTYMK, ZFC3H1, CBX2, PKM, TTC26, ATG10, TAGLN2, CD3EAP, SHISA9, SLC1A5, KPNA2, SCML2, E2F7, and SMARCD1, which were the independent risk factors for poor prognosis of HCC patients. In general, interference with AP003469.4 expression might delay the progression of HCC. AP003469.4 related network could help to identify the hub target molecules in HCC progression, which might be candidate biomarkers for evaluating the prognosis of HCC patients.

Keywords: AP003469.4; competing endogenous RNAs; disease-free survival; hepatocellular carcinoma; overall survival.