Hypomethylated RRBP1 Potentiates Tumor Malignancy and Chemoresistance in Upper Tract Urothelial Carcinoma

Abstract

Ribosome-binding protein 1 (RRBP1) is a potential oncogene in several cancer types. However, the correlation between RRBP1 expression and the prognosis of patients with upper tract urothelial carcinoma (UTUC) remains unclear. In this study, we identified that RRBP1 is associated with carcinogenesis and metastasis in UTUC using a methylation profiling microarray. High correlations between RRBP1 and cancer stages, nodal metastasis status, molecular subtypes, and prognosis in bladder urothelial cancer (BLCA) were found. Aberrant DNA methylation in the gene body region of RRBP1 was determined in UTUC tissues by methylation-specific PCR. RRBP1 expression was significantly increased in UTUC tissues and cell lines, as determined by real-time PCR and immunohistochemistry. RRBP1 depletion significantly reduced BFTC909 cell growth induced by specific shRNA. On the other hand, molecular subtype analysis showed that the expression of RRBP1 was associated with genes related to cell proliferation, epithelial–mesenchymal transition, and basal markers. A patient-derived organoid model was established to analyze patients’ responses to different drugs. The expression of RRBP1 was related to chemoresistance. Taken together, these results provide the first evidence that RRBP1 gene body hypomethylation predicts RRBP1 high expression in UTUC. The data highlight the importance of RRBP1 in UTUC malignancy and chemotherapeutic tolerance.

Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma

“…In addition, PDIA4 can promote the progression of malignant glioma through the PI3K/AKT/M‐TOR pathway [35]. Ribosome‐binding protein 1 (RRBP1) is a potential oncogene in several cancer types [36], including in oral [37], breast [38], and urothelial cancers. In urothelial carcinoma, methylated RRBP1 is associated with neoplastic biological behavior, and the abundance of methylation is associated with chemoresistance.…”

Prognosis Risk Model Based on Necroptosis-Related Signature for Bladder Cancer

“…The effect of RHBDD1 on BLCA is rarely studied, but its cancer-promoting role in colorectal cancer was confirmed in the study by Zhang M et al [ 56 ]. As for RRBP1, it was proven to be highly expressed in BLCA, and the correlation with migration and invasion was verified by various groups [ 57 , 58 , 59 ]. In addition, the effect of PALLD on BLCA is rarely studied, but Pogue-Geile KL et al proved that the palladin mutation could cause the tumor’s strong invasive and migratory abilities in pancreatic cancer [ 60 ].…”

DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma

“…The UM-UC-14 cell line was purchased from the European Collection of Authenticated Cell Cultures (ECACC). These cell lines were previously described in detail [20]. Tissue specimens of UTUC were collected from patients at the Chang Gung Memorial Hospital in Kaohsiung.…”

“…As one of the most abundant and well-studied epigenetic modifications, DNA methylation consists of the covalent addition of a methyl group at the carbon 5 position of the cytosine ring. DNA methylation is an important epigenetic modification in cancer and alters gene expression without changing the DNA sequence, typically hypermethylated tumor suppressor genes [18,19] and hypomethylating oncogenes [20].…”