Wnt/β-catenin signaling as an emerging potential key pharmacological target in cholangiocarcinoma

Qiu, Ling; Yang, Shijie; Wu, Jiacheng; Liu, Tongjun

doi:10.1042/bsr20193353

Cited by 23 publications

(20 citation statements)

References 84 publications

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“…WNT11 is notably upregulated in a liver injury model, and it may be arising from macrophages ( Jiang et al, 2019 ). Clinical and preclinical studies have shown that activation of the Wnt signaling pathway plays a key role in the induction and progression of cholangiocarcinoma ( Zhang et al, 2020 ). In bile duct-ligated mice, adenovirus carrying Dickkopf-1 (WNT antagonist) was able to significantly reduce cholangiocyte proliferation.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing

Xie

et al. 2021

Front. Genet.

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A choledochal cyst (CC) is a common congenital biliary disease in children, yet the underlying molecular bases for the cystic and fusiform clinical subtypes are unknown. RNA sequencing (RNA-seq) has been performed on 22 high-quality CC samples, including 12 cystic CC and 10 fusiform CC samples, to search for molecular features. Weighted gene co-expression network analysis (WGCNA) was performed to identify key modules associated with clinical subtypes. Bioinformatic analyses were conducted to elucidate potential mechanisms. Then, we constructed protein–protein interaction (PPI) networks to identify candidate hub genes related to CC. Finally, we used the support vector machine (SVM) to eliminate redundant features and screen out the hub genes. The selected gene expression was determined in CC patients through quantitative real-time polymerase chain reaction (PCR). A total of 6,463 genes were found to be aberrantly expressed between cystic CC and fusiform CC. Twelve co-expression modules that correlated with clinical subtypes of CC were identified and assigned representative colors. Among the 12 modules, the blue module was considered the key module. Two functionally distinct sets of dysregulated genes have been identified in two major subtypes, metabolism-related genes in cystic CC and immune-related genes in fusiform CC. A total of 20 candidate hub genes that were correlated with clinical subtypes were found in the blue module. In addition, we found ERBB2 and WNT11 that have not been studied in CC and verified their differential expression in CC through quantitative real-time PCR experiments. For the first time, we have described the transcriptome characteristics of CC. These results suggest that cystic CC and fusiform CC have different molecular mechanisms. The bi-omics-identified novel candidate genes and pathways might be helpful for personalized treatment and are of great clinical significance for CC.

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Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing

Xie

et al. 2021

Front. Genet.

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“…MiRNAs are known to play important roles in the progression of multiple diseases, including hepatic carcinoma (25,26). We found that a miR-513a-5p antagomir partially reversed the inhibitory effect of LINC01234 knockdown on liver cancer.…”

Section: Discussionmentioning

confidence: 73%

Knockdown of lncRNA LINC01234 suppresses the tumorigenesis of liver cancer via sponging miR-513a-5p

Song

et al. 2020

Preprint

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Background Liver cancer is a frequent malignancy with poor prognosis. It has been reported that many lncRNAs could regulate the progression of liver cancer. To identify potential therapeutic targets for liver cancer, we conducted bioinformatics analysis of lncRNAs in tumor tissues and adjacent normal tissues. Methods The differential expression of lncRNAs between liver cancer tissues and adjacent normal tissues were examined by bioinformatics analysis. Cell proliferation was tested by CCK-8. Cell apoptosis in liver cancer was detected by flow cytometry. Gene and protein expression in liver cancer cells were measured by q-PCR and Western-blot, respectively. Xenograft tumor model was established to verify the function of LNC01234 on liver cancer in vivo. Results LNC01234 was found to be notably upregulated in liver cancer tissues. In addition, knockdown of LNC01234 significantly inhibited the proliferation, invasion and induced the apoptosis of liver cancer cells. Meanwhile, miR-513a-5p was a downstream target of LNC01234 and USP4 was a direct target of miR-513a-5p. Moreover, downregulation of LNC01234 inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling. Conclusion Downregulation of LNC01234 could inhibit the progression of liver cancer, which may serve as a potential novel target for treatment of liver cancer.

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“…This suggested that the ClC-5 knockdown decreased the Wnt/β-catenin signal transduction pathway. Growing evidence suggests that inhibition of the Wnt/β-catenin signaling pathway can inhibit CCA progression ( 26 - 28 ). Furthermore, β-catenin degradation can activate the mitochondrial apoptotic pathway by promoting Bax translocation ( 29 - 31 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/β-catenin signaling pathway

Shi

Zhou

et al. 2022

BMB Rep

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Chloride channel-5 (ClC-5), an important branch of the ClC family, is involved in the regulation of the proliferation and cell-fate of a variety of cells, including tumor cells. However, its function in cholangiocarcinoma (CCA) cells remains enigmatic. Here, we discovered that ClC-5 was up-regulated in CCA tissues and CCA cell lines, while ClC-5 silencing inhibited CCA cell proliferation and induced apoptosis. Further mechanism studies revealed that ClC-5 inhibition could inhibit Wnt/β-catenin signaling activity and further activate the mitochondria apoptotic pathway in CCA cells. Furthermore, rescuing Wnt/β-catenin signaling activation eliminated the anti-tumor function of ClC-5 knockdown. Together, our research findings illustrated that ClC-5 inhibition plays an anti-tumor role in CCA cells via inhibiting the activity of the Wnt/β-catenin pathway, which in turn activates the mitochondrial apoptotic pathway. [BMB Reports 2022; 55(6): 299-304]

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Wnt/β-catenin signaling as an emerging potential key pharmacological target in cholangiocarcinoma

Cited by 23 publications

References 84 publications

Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing

Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing

Knockdown of lncRNA LINC01234 suppresses the tumorigenesis of liver cancer via sponging miR-513a-5p

Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/β-catenin signaling pathway

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