Dataset Information

RBM47 functions as an anti-oncogene by regulating expression and alternative splicing of cell proliferation and apoptosis associated genes in colorectal cancer cells

ABSTRACT: Transcriptional and post-transcriptional regulation that are mediated by RNA binding proteins (RBPs) have essential influence on the development and progression of colorectal cancer (CRC), while the underlying mechanisms need to be clarified. In this study, we focused on RNA Binding Motif Protein 47 (RBM47) and overexpressed its expression in HCT116 cells to evaluate its influence on cellular phenotypes and performed transcriptome sequencing (RNA-seq) to identify the downstream targets, including the expression and splicing changed genes. After RBM47 overexpression (RBM47-OE), we found the proliferation level was decreased while apoptosis level was increased. Meanwhile, the invasion and migration ability of HCT116 was also significantly inhibited by RBM47-OE. To further decipher the molecular targets of RBM47, we identified 216 up and 97 down differentially expressed genes (DEGs) by RBM47-OE, and found they were significantly enriched in immune response, apoptosis, TNF signaling, and autophagy pathways. At the same time, RBM47-OE can also regulate the splicing pattern of 2541 alternative splicing (AS) events. The regulated AS genes (RASGs) were enriched in cell cycle, DNA damage and repair, mRNA splicing, and cell division associated pathways, indicating that the downstream targets of RBM47 were tightly associated its cellular functions. To validate the regulation on gene expression and AS, we selected several DEGs and AS events to perform RT-qPCR experiment. The results showed that the expression level of CASP3, CCN1, and ATF5, and the splicing pattern of CD44 and MDM2, were significantly regulated by RBM47-OE in HCT116 cells. In summary, our results demonstrated the anti-tumor function and the globally downstream targets of RBM47 in CRC cells. We extend the cellular and molecular cognition of RBM47 in tumor. The identified molecular targets can also be served as potential targets for CRC treatment in future.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282110 | GEO | 2025/07/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Papillary thyroid cancer (PTC) is an ever-increasing cancer type worldwide, and greatly decreases the life quality and affects survival time of patients during its development and progression, but the underlying mechanisms and key factors for PTC progression are not clear. Recent studies demonstrated the potassium channel protein SK4, also named as KCNN4, participates in the progression of many cancers, while it lacks the molecular mechanism study for SK4 function. In this study, we performed functional and molecular explorations for SK4 by overexpressing its level in thyroid cancer BHT101 cells. Cellular proliferation and invasion experiments were performed to assess the influences of SK4 on cell behaviors. Further, whole transcriptome sequencing (RNA-seq) analysis helped us systematically investigated the down stream targets of SK4, including differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs). We finally validated several DEGs and RASEs associated with the functions of SK4 by RT-qPCR experiment. In thyroid cancer patients, SK4 expression was completely lost in normal tissues and significantly increased in every stage of tumor tissues compared with normal tissues, the reason of which probably results from the low DNA methylation level at its promoter region. Consistent with previous study, SK4 overexpression (SK4-OE) promoted proliferation level and invasion ability of BHT10 cells compared with negative control (NC). By analyzing the RNA-seq data, we detected dozens of DEGs and found that up DEGs were enriched in negative regulation of apoptotic progress, including VTCN1, MSX1, FATE1, TEK, and PRAMEF2. More importantly, we found SK4-OE globally changed the alternative splicing pattern and identified 1639 RASEs. The genes of RASEs were enriched in DNA damage/repair, viral process, translation, and mRNA splicing pathways, which were tightly associated with the pathogenesis and progression of cancers. The splicing regulatory genes from RASGs could partly explain the reason of global AS dysregulation by SK4-OE in BHT101 cells. Finally, we validated several DEGs and RASEs associated with PTC progression by RT-qPCR. We found the expression of VTCN1, EDN1, SLC29A4, RP11-473M20.16, and CH507-513H4.4 were validated by RT-qPCR, as well as the AS pattern of TMEM116, RBM39, and RBM6. In summary, our results deeply explored the molecular targets of SK4 associated them with SK4-induced progression of PTC. We highlight that SE4-regulated AS pattern probably is a novel regulatory mechanism for SK4 in PTC. The identified DEGs and RASEs, as well as SK4 itself, could be used as potential therapeutic targets for PTC treatment in future.

Dataset Information

RBM47 functions as an anti-oncogene by regulating expression and alternative splicing of cell proliferation and apoptosis associated genes in colorectal cancer cells

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets