Ring finger protein 43 expression is associated with genetic alteration status and poor prognosis among patients with intrahepatic cholangiocarcinoma

Talabnin, Chutima; Patcharee, Janthavon; Thongsom, Sunisa; Suginta, Wipa; Talabnin, Krajang; Wongkham, Sopit

doi:10.1016/j.humpath.2015.12.027

Cited by 12 publications

(16 citation statements)

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“…Despite its potential role as a tumour suppressor gene in various cancer types, the biological function of RNF43 in CCA has never been thoroughly explored. Our previous study on CCA tissues reported that low RNF43 expression was localised in the nucleus ( 19 ). The current study confirmed a low expression of RNF43 at both the mRNA and protein levels in all CCA cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Inactivating mutation of RNF43 is reported in several types of cancers, including CCA. Patients with CCA with the inactivating RNF43 mutation and/or downregulation of RNF43 expression exhibit less favourable survival outcomes, suggesting that RNF43 may function as a tumour suppressor gene ( 10 , 19 ). Despite its potential role as a tumour suppressor gene in various cancer types, the biological function of RNF43 in CCA has never been thoroughly explored.…”

Section: Discussionmentioning

confidence: 99%

“…After 48 h of transfection, cells were washed with 1X PBS then lysis buffer was added [150 mM NaCl; 50 mM Tris-HCl pH 7.4; 1% Sodium deoxycholate; 0.1% SDS; and 1X Protease inhibitor cocktail (Roche Diagnostics)]. The whole-cell lysate was harvested ( 19 ). A nuclear extraction kit (cat.…”

Section: Methodsmentioning

confidence: 99%

“…The loss of endogenous RNF43 expression also enhances proliferation and the invasive capacity of gastric and colorectal cancer cells ( 18 ). Inactivating the mutation and downregulating RNF43 are associated with a less favourable survival of patients with CCA ( 10 , 19 ). Since a functional analysis of RNF43 in CCA has not yet been performed, this present aimed to determine the functional role of RNF43 in CCA and its underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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RNF43 overexpression attenuates the Wnt/β‑catenin signalling pathway to suppress tumour progression in cholangiocarcinoma

et al. 2021

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RING finger protein 43 ( RNF43 ) is a ubiquitin E3 ligase that negatively regulates Wnt/β-catenin signalling. Mutation, inactivation and downregulation of RNF43 in cholangiocarcinoma (CCA) are associated with a less favourable prognosis. Since the functional role of RNF43 in CCA has not yet been demonstrated, the present study aimed to assess the effect of its overexpression in mediating CCA suppression via Wnt/β-catenin signalling pathway inhibition. Accordingly, RNF43 was overexpressed, and various malignant phenotypic changes studied, including cell proliferation, cell migration, chemotherapeutic sensitivity and the expression of several Wnt/β-catenin target genes. Overexpression of RNF43 in the CCA cell-line KKU-213B hindered activation of Wnt/β-catenin signalling, evidenced by: i) Accumulation of β-catenin in the cytoplasmic fraction and downregulation of several known Wnt target genes at the mRNA level [ AXIN2 , survivin ( BIRC5 ), CCND1, MMP-7, c-MYC and ABCB1 ( MDR1 )]; ii) a reduction of cell proliferation; iii) a significant decrease in KKU-213B cell migration with RNF43 overexpression via upregulation of E-cadherin ( CDH1 ); and iv) a reduction in N-cadherin ( CDH2 ), MMP-2, MMP-7 and MMP-9 . In addition, overexpression of RNF43 increased 5-fluorouracil sensitivity and downregulation of ABC transporter genes [including ABCB1 and ABCC1 (MRP1)]. The current results demonstrate a functional role for RNF43 in CCA by: i) Blocking β-catenin nuclear translocation; and ii) the subsequent downregulation of Wnt/β-catenin target genes (the latter being involved in the progression of CCA and chemotherapeutic drug susceptibility). Therefore, the present findings suggest that RNF43 could serve a tumour suppressive role in CCA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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RNF43 overexpression attenuates the Wnt/β‑catenin signalling pathway to suppress tumour progression in cholangiocarcinoma

et al. 2021

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“…Previous studies have shown that polymorphisms of genes or proteins were associated with survival in CRC patients, with or without chemotherapy (Huang et al, 2017;Okazaki et al, 2017;Yeh et al, 2017;Zhu et al, 2017), including TLR7, vitamin D, and calcium-sensing receptor (BCL2). Moreover, Hitomi (Sakamoto et al, 2015) and Talabnin (Talabnin et al, 2016) found RNF43 mutation might downregulate gene expression and was related to the poor prognosis of intrahepatic cholangiocarcinoma patients. However, we observed that there was a significant difference between the two groups in OS.…”

Section: Discussionmentioning

confidence: 99%

Reduced Frequency and Prognostic Significance of Ring Finger Protein 43 Nucleotide Polymorphisms in a Chinese Colorectal Cancer Cohort

Wen

Wang

Huang

et al. 2019

DNA and Cell Biology

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The aim of this research was to verify the mutation rate of the ring finger protein 43 (RNF43) of the transmembrane E3 ubiquitin ligase and investigate the influence of single nucleotide polymorphisms (SNPs) rs2257205 in RNF43 in a Chinese colorectal cancer (CRC) cohort. DNA from 177 diagnosed CRC patients' tissues or blood samples were extracted, amplified, and sequenced. Clinicopathological features, including age, gender, tumor location, tumor-lymph node-metastasis stage, and survival information, were analyzed. Four novel RNF43 mutations (including G659 and R117 sites) were validated in 177 CRC patients; all events were somatic frameshift mutations. Furthermore, we also found that an SNP (rs2257205) of the RNF43 X117 site was associated with overall survival (OS) instead of disease-free survival. G homozygote subjects were significantly correlated with poor OS compared with another group. Then we rescued RNF43 R117R (encoded by nucleotide CGC) and R117H (encoded by nucleotide CAC) expression in the HCT116 cells and analyzed the targets of the Wnt/b-catenin pathway. The expression of CCND1 and c-Myc were decreased. The prognosis of CRC patients could be affected by the different functions of SNPs of RNF43.

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Combining expression of RNF43 and infiltration level of CD163⁺ tumor associated macrophage predicts prognosis of clear cell renal cell carcinoma

Zhu

Shi

Tian³

et al. 2022

Cancer Medicine

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Searching for reliable indicators for evaluating prognosis diagnosed with clear cell renal cell carcinoma (ccRCC) is crucial for improving clinical therapies.However, current researches have looked mainly at the prognostic value of a single intratumoral indicator, neglecting tumor-infiltrating immune cells (TIICs) in the microenvironment. This study examined whether the integration of Ring finger protein 43 (RNF43) expression and CD163 + tumor-associated macrophage (TAM) infiltration in combination with clinical indexes forecast ccRCC patient outcome with relatively high accuracy. Firstly, the expression of RNF43 and CD163 were detected with immunohistochemistry. Totally, 346 ccRCC patients were random separated evenly into training and validation datasets to make further analyses. We found that RNF43 expression was negatively correlated with infiltration level of CD163 + TAM in ccRCC, which was closely associated with the TNM stage and outcome of these patients. The multiple regression analysis demonstrated that RNF43, CD163, and TNM stage could function as independent risk factors in overall survival (OS) and progression-free survival (PFS) prediction of ccRCC. Furthermore, a better postoperative prognosis index for ccRCC patients was obtained by combining RNF43 and CD163 + TAMs, which assessed with time-dependent C-index analyses and a nomogram. Consequently, combining RNF43 and CD163 + TAMs along with TNM stage acquired robust accuracy in forecasting outcome of patients with ccRCC. In conclusion, combining intratumoral RNF43 expression, CD163 + TAM infiltration, and TNM stage could significantly enhance the veracity in forecasting postoperative outcomes.

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Ring finger protein 43 expression is associated with genetic alteration status and poor prognosis among patients with intrahepatic cholangiocarcinoma

Cited by 12 publications

References 30 publications

RNF43 overexpression attenuates the Wnt/β‑catenin signalling pathway to suppress tumour progression in cholangiocarcinoma

RNF43 overexpression attenuates the Wnt/β‑catenin signalling pathway to suppress tumour progression in cholangiocarcinoma

Reduced Frequency and Prognostic Significance of Ring Finger Protein 43 Nucleotide Polymorphisms in a Chinese Colorectal Cancer Cohort

Combining expression of RNF43 and infiltration level of CD163⁺ tumor associated macrophage predicts prognosis of clear cell renal cell carcinoma

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Ring finger protein 43 expression is associated with genetic alteration status and poor prognosis among patients with intrahepatic cholangiocarcinoma

Cited by 12 publications

References 30 publications

RNF43 overexpression attenuates the Wnt/β‑catenin signalling pathway to suppress tumour progression in cholangiocarcinoma

RNF43 overexpression attenuates the Wnt/β‑catenin signalling pathway to suppress tumour progression in cholangiocarcinoma

Reduced Frequency and Prognostic Significance of Ring Finger Protein 43 Nucleotide Polymorphisms in a Chinese Colorectal Cancer Cohort

Combining expression of RNF43 and infiltration level of CD163+ tumor associated macrophage predicts prognosis of clear cell renal cell carcinoma

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Combining expression of RNF43 and infiltration level of CD163⁺ tumor associated macrophage predicts prognosis of clear cell renal cell carcinoma