Ubiquitination-Related miRNA–mRNA Interaction Is a Potential Mechanism in the Progression of Retinoblastoma

Abstract

PURPOSE. Retinoblastoma (RB) is the most common primary malignant intraocular cancer. The etiology of RB is complex, and the mechanisms driving its progression remain unclear. Here, we used a series of bioinformatics approaches and experimental methods to investigate the potential regulatory mechanism involved in RB progression. METHODS.The common differentially expressed genes were obtained from the public dataset GSE97508. Protein-protein interaction (PPI) network, correlation, and functional enrichment analyses were carried out. The candidate genes were verified in different RB cell lines, and ARPE19 cells served as control. miRNA-mRNA interaction analysis was performed and confirmed by real-time PCR. The CCK-8 assay was conducted to detect cell viability, and the transwell assay was utilized for evaluating the abilities of cell migration and invasion. RESULTS.Overall, a total of 258 common differentially expressed genes associated with RB progression were screened out. The PPI network analysis further identified eight downregulated genes mainly enriched in the protein ubiquitination pathway. Moreover, we confirmed UBE2E1, SKP1, FBXO9, FBXO15, and RNF14 from among eight genes through experimental validation in vitro. Furthermore, miRNA-mRNA interaction and real-time PCR analysis of five hub genes revealed that ubiquitination-related miR-548k was involved in RB progression. Loss-and gain-of-function experiments demonstrated that miR-548k and its targets were essential for cell viability, migration, and invasion in the RB cells. CONCLUSIONS.Our data indicate that the dysregulation of protein ubiquitination may play an important role in RB progression, and ubiquitination-related miR-548k may be a promising therapeutic target for RB.

Prognostic Signature, Immune Features, and Therapeutic Responses of a Novel Ubiquitination-Related Gene Signature in Lung Adenocarcinoma

“…Therefore, addressing defective parts of the ubiquitin system as a potential treatment for inflammatory diseases, malignancies, and infectious diseases is an approach that holds a lot of promise. Furthermore, the creation of targetable molecular subtypes and risk stratification tools by making use of ubiquitination-related genes (UbRGs) has a great deal of promise [ 17 , 18 ]. On the other hand, as far as we are aware, there are no studies done in the past that investigated whether there was a correlation between ubiquitination and the prognostic evaluation and molecular subtypes of LUAD.…”

Ferroptosis in the Lacrimal Gland Is Involved in Dry Eye Syndrome Induced by Corneal Nerve Severing

“…After conducting the normalization and background correction of data, the probe level data were converted into gene expression values. 26 The average expression value was taken as the gene expression value for multiple probes corresponding to a single gene. Principal component analysis observed the distribution patterns of trephined, contralateral, and control groups.…”

Identification of non-coding RNAs and their functional network associated with optic nerve invasion in retinoblastoma

“…Generally, ncRNAs can be divided into several types, including microRNA (miRNA), long ncRNA (lncRNA), circular RNA (circRNA), endogenous small interfering RNA, Piwi-associated small RNA, small nucleolar RNA (snoRNA), sno-derived RNA, transcription-initiation RNA, and miRNA-offset RNA [ 12 ]. Among them, miRNA, lncRNA and circRNA have attracted considerable interest and have been proven to be closely related to tumor progression [ [13] , [14] , [15] , [16] ]. Perineural invasion (PNI) is an aggressive form of cancer cell invasion along nerves that occurs in many malignant tumors [ 17 ].…”