Background: Hepatocellular carcinoma (HCC) is a very common neoplasm worldwide, and competitive endogenous RNA (ceRNA) plays an important role in the development of HCC. The purpose of this study is to investigate the molecular mechanisms of ceRNAs in HCC. Methods: This study detects potential ceRNAs from HCC through whole genome analysis of lncRNA, miRNA and mRNA expression. We then performed high-throughput sequencing of tissues from five hepatitis B related HCC patients to screen ceRNAs and those screened ceRNAs expressions were verified on tissues from an independent group of six patients. Finally, the function of ceRNAs of interest was illustrated in vitro. Result: Functional and pathway analysis of The Cancer Genome Atlas revealed ceRNA networks. The high-throughput sequencing identified 985 upregulated and 1612 downregulated lncRNAs and 887 upregulated and 1116 downregulated mRNAs in HCC patients. Differentially expressed genes were parallel to cancer-associated processes, comprising 18 upregulated and 35 downregulated significantly enriched pathways including alcoholism and viral carcinogenesis. Among them, a potential ceRNA network was detected and verified in six HCC patients. CeRNAs of the lncRNA MAGI2-AS3/miR-374-5p/FOXO1 pathway were significantly dysregulated in HCC, and validation in vitro showed that FOXO1 is positively regulated by MAGI2-AS3 through the induction of miR-374a/b-5p in HCC cells. In addition, the overexpression of FOXO1 is associated with proliferation, migration, and invasion of HCC cells and increases apoptosis of HCC cells. MiR-374a/b-5p caused an opposite effect by directly suppressing FOXO1 in HCC cells. Conclusion: CeRNA networks were found in HCC and aberrantly expressed ceRNAs of lncRNA MAGI2-AS3/miR-374-5p/FOXO1 plays a crucial role in HCC, assisting in diagnosis and providing a method for treatment.

Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.

Background: RAN binding protein 3‐like (RANBP3L), a member of the Ran‐binding protein family, has been linked to various cellular functions, but the role in cancer remains underexplored. In this research, we assessed the diagnostic and prognostic value of RANBP3L in pan‐cancer, especially in liver hepatocellular carcinoma (LIHC). Aims: This study aimed to explore the pan‐cancer expression, prognostic value, and immune‐related roles of RANBP3L, especially emphasis on validating its diagnostic and prognostic significance in hepatocellular carcinoma. Methods: We analyzed RANBP3L expression of 33 cancer types from TCGA data and assessed its relationship with overall survival (OS), disease‐specific survival (DSS), and progression‐free interval (PFI). We used TIMER2.0 and CIBERSORT to explore the correlation between RANBP3L expression and immune cells. We conducted immunohistochemistry, qRT‐PCR, and western blotting by using tissue samples from LIHC patients to assess the RANBP3L's diagnostic and prognostic value of LIHC. Results: In 18 different cancers, RANBP3L expression was found to be lower in tumor tissues compared to normal tissues, including LIHC. Lower RANBP3L expression was related to shorter OS, DSS, and PFI in LIHC. ROC analysis and the nomogram model based on RANBP3L expression demonstrated high predictive accuracy for patient diagnosis and survival. Moreover, immune infiltration analysis showed that RANBP3L was related to various immune cells and impacted prognosis. Furthermore, analysis of LIHC patient tissues found that higher RANBP3L expression was related to better tumor‐free survival and OS. Conclusion: RANBP3L plays a crucial role in LIHC. Not only does its expression level correlate with patient survival, but it also plays an important role in immune modulation. RANBP3L presents a promising candidate for future therapeutic strategies and a biomarker for LIHC.