Overexpression of Opa interacting protein�5 increases the progression of liver cancer via BMPR2/JUN/CHEK1/RAC1 dysregulation

Abstract

Opa interacting protein 5 (OIP5) overexpression is associated with human carcinoma. However, its biological function, underlying mechanism and clinical significance in liver cancer remain unknown. In the present study, the effects of OIP5 expression on liver cancer, and the mechanisms regulating these effects, were investigated. OIP5 expression was measured in human hepatocellular carcinoma (HCC) tissues and liver cancer cell lines. The effect of OIP5 knockdown on tumorigenesis was also detected in nude mice, and differentially-expressed genes (DEGs) were identified and their biological functions were identified. The results indicated that OIP5 expression was significantly upregulated in HCC tissues and four liver cancer cell lines (P<0.01). Increased OIP5 protein expression significantly predicted reduced survival rate of patients with HCC (P<0.01). OIP5 knockdown resulted in the suppression of proliferation and colony forming abilities, cell cycle arrest at the G0/G1 or G2/M phases, and promotion of cell apoptosis. A total of 628 DEGs, including 87 upregulated and 541 downregulated genes, were identified following OIP5 knockdown. Functional enrichment analysis indicated that DEGs were involved in ‘RNA Post-Transcriptional Modification, Cancer and Organismal Injury and Abnormalities’. Finally, OIP5 knockdown in Huh7 cells dysregulated bone morphogenetic protein receptor type 2/JUN/checkpoint kinase 1/Rac family small GTPase 1 expression. In conclusion, the overall results demonstrated the involvement of OIP5 in the progression of liver cancer and its mechanism of action.

Promoting cell proliferation, cell cycle progression, and glycolysis: Glycometabolism‐related genes act as prognostic signatures for prostate cancer

“…OIP5 was found to be highly expressed in many types of cancer. Studies have confirmed its role in the progression of hepatocellular, bladder, and gastric cancers 35–37 . Interestingly, OIP5 was also recognized as a downstream gene of E2F1 in the tumorigenesis and metastasis of glioblastoma, 38 which is consistent with the GSEA enrichment to E2F target in our study (Figure S3A,B).…”

Rac1, A Potential Target for Tumor Therapy

“…It can induce melanocytes to transform into mesenchymal-like cells, inhibit apoptosis, and enhance tumorigenesis (81). OPA interacting protein-5 (OIP5) regulates proliferation, apoptosis and cell cycle of HCC cells by influencing BMPR2-JUN-CHEK1-Rac1 signal axis (82).…”

Opa-Interacting Protein 5 Expression in Human Glioma Tissues Is Essential to the Biological Function of U251 Human Malignant Glioma Cells

“… 13 Using siRNA-mediated knockdown studies, we found that OIP5 silencing significantly inhibits glioma cell survival. Previous studies have shown that the JAK2/STAT3 pathway in nasopharyngeal carcinoma, 18 BMPR2/JUN/CHEK1/RAC1 in liver cancer, 19 miR-139-5p/NOTCH1 in breast cancer, 12 and mTORC2 and p38/PTEN in hepatocellular carcinoma, 20 and E2F1 signaling in glioblastoma 21 are involved in OIP5-regulated tumor progression. These pathways are primarily associated with tumor cell proliferation and migration.…”