Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma

Jia, Jia; Yang, Yanguo; Yan, Tingting; Chen, Tao; Guang-xin, LU

doi:10.4149/gpb_2020009

Cited by 6 publications

(8 citation statements)

References 24 publications

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“…We have shown here that in HGSOC cells, RFWD3 deficiency can lead to an accumulation of cells in G2/M phase, indicating a potential checkpoint block. This has also been previously reported in gastric cancer cells ( 21 ). A third group have reported a trend towards increased proportion of cells in G2/M phase in the U20S osteosarcoma cell line ( 18 ), however this only achieved statistical significance with one siRNA tested.…”

Section: Discussionsupporting

confidence: 88%

“…RFWD3 has been previously reported to participate in non-canonical signalling pathways distinct from its role in ICL repair in other cancer types ( 21 , 22 ). Therefore, the effect of RFWD3 deficiency on cancer relevant phenotypes was assessed using the RFWD3 Δ/Δ cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…This may be a result of the dysregulated cell cycle we observed in this cell line, with accumulation in G2/M phase leading to inhibition of cell growth. In gastric and colorectal cancer, RFWD3 was also associated with a cell migratory phenotype ( 21 , 22 ). Interestingly, these factors are thought to be linked to a signalling role of RFWD3 separate from the roles it plays in DNA damage repair.…”

Section: Discussionmentioning

confidence: 99%

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RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer

Taylor,

Hollis,

Gourley

et al. 2024

Front. Oncol.

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BackgroundDNA damage repair is frequently dysregulated in high grade serous ovarian cancer (HGSOC), which can lead to changes in chemosensitivity and other phenotypic differences in tumours. RFWD3, a key component of multiple DNA repair and maintenance pathways, was investigated to characterise its impact in HGSOC.MethodsRFWD3 expression and association with clinical features was assessed using in silico analysis in the TCGA HGSOC dataset, and in a further cohort of HGSOC tumours stained for RFWD3 using immunohistochemistry. RFWD3 expression was modulated in cell lines using siRNA and CRISPR/cas9 gene editing, and cells were characterised using cytotoxicity and proliferation assays, flow cytometry, and live cell microscopy.ResultsExpression of RFWD3 RNA and protein varied in HGSOCs. In cell lines, reduction of RFWD3 expression led to increased sensitivity to interstrand crosslinking (ICL) inducing agents mitomycin C and carboplatin. RFWD3 also demonstrated further functionality outside its role in DNA damage repair, with RFWD3 deficient cells displaying cell cycle dysregulation, reduced cellular proliferation and reduced migration. In tumours, low RFWD3 expression was associated with increased tumour mutational burden, and complete response to platinum chemotherapy.ConclusionRFWD3 expression varies in HGSOCs, which can lead to functional effects at both the cellular and tumour levels.

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer

Taylor,

Hollis,

Gourley

et al. 2024

Front. Oncol.

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“…In addition, aberrant activation of UBE2C enhanced cell proliferation, clonogenicity, and invasive growth of NSCLC [ 31 ]. Jia et al reported that RFWD3 was overexpressed in gastric carcinoma, and its knockdown inhibited the proliferation and migration of gastric carcinoma cells through modulating AKT, ERK/P38, and Slug pathways [ 32 ]. In the current research study, we used the mRNA expression data of 71 UbRGs from the TCGA datasets and the LASSO regression analysis to construct a 9-UbRGs predictive signature.…”

Section: Discussionmentioning

confidence: 99%

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

Gong

2022

Journal of Oncology

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Growing studies have implicated the association of ubiquitination-related genes (UbRGs) with the cancer progression and the long-term survival of patients. However, the prognostic values of UbRGs in lung adenocarcinoma (LUAD) have not been investigated. Our study aimed to establish a ubiquitination-related model for prognosis prediction and internal mechanism investigation. The transcriptome expression profiles and corresponding clinical information of LUAD were obtained from TCGA and GEO datasets. Differentially expressed genes (DEGs) were screened between LUAD specimens and nontumor specimens. Kaplan–Meier analysis and univariate assays were carried out on DEGs to preliminarily screen survival-related UbRGs. Then, the LASSO Cox regression model was applied to develop a multigene signature, which was then demonstrated in two GEO datasets by the use of Kaplan-Meier, ROC, and Cox analyses. We estimated the immune cell infiltration in tumor microenvironment via CIBERSORT and immunotherapy response through the TIDE algorithm. In this study, a total of 71 ubiquitination-related DEGs were identified. Nine UbRGs, including TUBA4A, TRIM2, PLK1, ARRB1, TRIM58, PLK1, ARRB1, CCNB1, TRIM6, PTTG1, and CCT2, were included to establish a risk model, which was validated in TCGA and GEO datasets. The multivariate assays demonstrated that the 9-UbRGs signature was a robust independent prognostic factor in the overall survival of LUAD patients. The abundance of CD8 T cells, activated CD4 T memory cells, resting NK cells and macrophages was higher in the high-risk group, and the TMB of high-risk group was statistically higher than the low-risk group. Multiple drugs approved by FAD, targeting UbRGs, were available for the treatment of LUAD. Overall, we identified a nine ubiquitination-related gene signature, and the signature may be applied to be a potential biomarker for CD8 T cells response and clinical responses to immune checkpoint inhibitors for LUAD.

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“…Subsequent studies demonstrated that RFWD3 is an E3 ubiquitin ligase that positively regulates p53 levels in response to DNA damage ( Fu et al, 2010 ). The published literature mentioned that the high expression of RFWD3 was involved in the occurrence and development of gastric carcinoma, and may be an important poor prognostic factor of gastric carcinoma ( Jia et al, 2020 ). Our present study, through IHC analysis and TCGA database, indicated that RFWD3 expression was significantly higher in CRC tissues compared with matched para-tumorous tissues.…”

Section: Discussionmentioning

confidence: 99%

RFWD3 Participates in the Occurrence and Development of Colorectal Cancer via E2F1 Transcriptional Regulation of BIRC5

Xiao

Fan

et al. 2021

Front. Cell Dev. Biol.

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Objectives: Colorectal cancer (CRC) is one of the most common human malignancies. It was reported that the alterations in the DNA damage response (DDR) pathways are emerging as novel targets for treatment across different cancer types including CRC. RFWD3 plays a critical role in replication protein A (RPA)-mediated DNA damage in cancer cells. More importantly, RFWD3 can response to DNA damage by positively regulating p53 stability when the G1 cell cycle checkpoint is activated. However, the functional significance of RFWD3 in CRC has not been reported in the existing documents.Materials and Methods: Here, we revealed high expression of RFWD3 in CRC tissues by IHC analysis and The Cancer Genome Atlas (TCGA) database. Besides, overexpression of RFWD3 in CRC cell lines was also confirmed by qRT-PCR and western blot assay. The Celigo cell counting method and wound-healing/transwell migration assay were applied to evaluate CRC cell proliferation and migration. The tumor growth indicators were quantified in nude mice xenografted with shRFWD3 and shCtrl RKO cells.Results: The results indicated that RFWD3 knockdown restricted CRC development in vitro and in vivo. In exploring the downstream mechanism of RFWD3’s action, we found that RFWD3 could transcriptionally activate BIRC5 by interacting with E2F transcription factor 1 (E2F1). Accordingly, we identified BIRC5 as a downstream gene of RFWD3 regulating CRC. Subsequent loss- and gain- of function experiments demonstrated that upon overexpressing BIRC5 in RKO cells with down-regulated RFWD3, the inhibitory effects of cell proliferation, migration and colony formation could be reversed, while the capacity of cell apoptosis was ameliorated, suggesting that the effects of RFWD3 depletion was mainly due to BIRC5 suppression.Conclusion: Taken together, this study revealed that RFWD3 participates in the occurrence and development of colorectal cancer via E2F1 transcriptional regulation of BIRC5.

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Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma

Cited by 6 publications

References 24 publications

RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer

RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer

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

RFWD3 Participates in the Occurrence and Development of Colorectal Cancer via E2F1 Transcriptional Regulation of BIRC5

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