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A CTCF mediated intrachromosomal looping of RB1 promoter and its downstream silencer served as a regulatory inducer to inactivate RB1, revealing a novel transcriptional mechanism underlying RB1 dysfunction independent of gene mutation.

Recent studies have reported that T-cell differentiation protein 2 (MAL2) is an important regulator in cancers. Here, we downloaded data from multiple databases to analyze MAL2 expression and function in pan-cancers, especially in ovarian cancer (OC). Gene Expression Profiling Interactive Analysis (GEPIA) databases was used to examine MAL2 expression in 13 types of cancer. Kaplan–Meier plotter database was used to analyze the overall survival rate of MAL2 in pan-cancers. The Catalog of Somatic Mutations in Cancer (COSMIC), cBioPortal, and UCSC databases were used to examine MAL2 mutation in human cancers. Metascape, STRING, and GeneMANIA websites were used to explore MAL2 function in OC. Furthermore, ggplot2 package and ROC package were performed to analyze hub gene expression and undertake receiver operating characteristic (ROC) analysis. Drug sensitivity of MAL2 in OC was examined by the GSCALite database. In order to verify the results from databases above, real-time quantitative polymerase chain reaction (qRT-PCR) and western blotting were conducted to detect the expression of MAL2 in OC cells. CRISPR/Cas9 system was used to knockout the MAL2 gene in the OC cell lines HO8910 and OVCAR3, using specific guide RNA targeting the exons of MAL2. Then, we performed proliferation, colony formation, migration, and invasion assays to investigate the impact of MAL2 in OC cell lines in vivo and in vitro. Epithelial-mesenchymal transition (EMT)-associated biomarkers were significantly altered in vitro via western blotting and qRT-PCR. Taken together, we observed that MAL2 was remarkably dysregulated in multiple cancers and was related to patient overall survival (OS), mutation, and drug sensitivity. Furthermore, experimental results showed that MAL2 deletion negatively regulated the proliferation, migration, invasion, and EMT of OC, indicating that MAL2 is a novel oncogene that can activate EMT, significantly promote both the proliferation and migration of OC in vitro and in vivo, and provide new clues for treatment strategies.

Chromatin-enriched RNAs (cheRNAs) constitute a special class of long noncoding RNAs (lncRNAs) that are enriched around chromatin and function to activate neighboring or distal gene transcription. Recent studies have shown that cheRNAs affect chromatin structure and gene expression by recruiting chromatin modifiers or acting as bridges between distal enhancers and promoters. The abnormal transcription of cheRNAs plays an important role in the occurrence of many diseases, particularly tumors. The critical effect of cancer stem cells (CSCs) on the formation and development of tumors is well known, but the function of cheRNAs in tumorigenesis, especially in CSC proliferation and stemness maintenance, is not yet fully understood. This review focuses on the mechanisms of cheRNAs in epigenetic regulation and chromatin conformation and discusses the way cheRNAs function in CSCs to deepen the understanding of tumorigenesis and provide novel insight to advance tumor-targeting therapy.