Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription

Chen, Qinjunjie; Wang, Haibo; Li, Zheng; Li, Fengwei; Liang, Leilei; Zou, Yiran; Shen, Hao; Li, Jun; Xia, Yong; Cheng, Zhangjun; Yang, Tian; Wang, Kui

doi:10.1016/j.jhep.2021.08.027

Cited by 145 publications

(96 citation statements)

References 39 publications

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“…A previous study demonstrated that circ-CCAC1 elevated YY1 expression to promote cholangiocarcinoma (CCA) by sponging miR-514a-5p in CCA cells while elevating SH3GL2 expression to enhance cell permeability by directly sequestering EZH2 in the cytoplasm of human umbilical vein endothelial cells [ 46 ]. Depending on the different subcellular locations, circACTN4 could interact with YBX1 to coactivate the transcription of FZD7 in the nucleus and sponge miR-424-5p to upregulate the mRNA level of YAP1 in the cytoplasm, thereby facilitating the development and progression of intrahepatic cholangiocarcinoma [ 47 ]. Interestingly, we revealed the dual mechanism of circRNA in the cytoplasm; this was the study report to reveal that circFARP1 accurately and cooperatively regulates the expression and secretion of LIF, implying that circRNAs collaborate in the TME to drive tumor chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis

Xia

Zhang

et al. 2022

Mol Cancer

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Background Cancer-associated fibroblasts (CAFs) are critically involved in gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanism by which CAFs promote chemotherapy resistance remains unexplored. Here, we explored the role of circRNAs in CAF-induced GEM resistance in PDAC. Methods circRNA sequencing and quantitative real-time PCR (qRT–PCR) were utilized to screen CAF-specific circRNAs. The effects of CAF circFARP1 expression on GEM resistance in tumor cells were assessed in vitro and in vivo. RNA-seq, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays were used to screen the downstream target and underlying mechanism of circFARP1. Results circFARP1 (hsa_circ_0002557), a CAF-specific circRNA, was positively correlated with GEM chemoresistance and poor survival in an advanced PDAC cohort. Silencing or overexpressing circFARP1 in CAFs altered the ability of CAFs to induce tumor cell stemness and GEM resistance via leukemia inhibitory factor (LIF). Mechanistically, we found that circFARP1 directly binds with caveolin 1 (CAV1) and blocks the interaction of CAV1 and the E3 ubiquitin-protein ligase zinc and ring finger 1 (ZNRF1) to inhibit CAV1 degradation, which enhances LIF secretion. In addition, circFARP1 upregulated LIF expression by sponging miR-660-3p. Moreover, high circFARP1 levels were positively correlated with elevated serum LIF levels in PDAC and poor patient survival. Decreasing circFARP1 levels and neutralizing LIF significantly suppressed PDAC growth and GEM resistance in patient-derived xenograft models. Conclusions The circFARP1/CAV1/miR-660-3p/LIF axis is critical for CAF-induced GEM resistance in PDAC. Hence, circFARP1 may be a potential therapeutic target for PDAC.

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Section: Discussionmentioning

confidence: 99%

circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis

Xia

Zhang

et al. 2022

Mol Cancer

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“…Interestingly, a novel circFAT1(e2) interacts with YB-1 protein in the nucleus and inhibits gastric cancer progression [ 148 ]. Likewise, in intrahepatic cholangiocarcinoma, circACTN4 also interacts with YB-1 and co-initiates the transcription of the downstream target FZD7 , promoting the progression of intrahepatic cholangiocarcinoma [ 149 ].…”

Section: Upstream Regulation Of Yb-1mentioning

confidence: 99%

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

Yin

Zheng

Luo

et al. 2022

Cells

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Y box binding protein 1 (YB-1) is a protein with a highly conserved cold shock domain (CSD) that also belongs to the family of DNA- and RNA-binding proteins. YB-1 is present in both the nucleus and cytoplasm and plays versatile roles in gene transcription, RNA splicing, DNA damage repair, cell cycle progression, and immunity. Cumulative evidence suggests that YB-1 promotes the progression of multiple tumor types and serves as a potential tumor biomarker and therapeutic target. This review comprehensively summarizes the emerging functions, mechanisms, and regulation of YB-1 in cancers, and further discusses targeted strategies.

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“…Recent studies have shown that ICC is mainly derived from epithelial cells of the biliary tract in the liver. In the process of tumorigenesis, some genetic changes have been identified, such as IDH1/2, FGFRs, EGFRs, KRAS, and BRAF [ 1 ], which lead to the dysregulation of some fetal cell survival pathways, such as RAS-RAF-MEK-ERK signaling or PI3K-AKT-mTOR signaling [ 4 ]. Although some mechanisms underlying the carcinogenesis of ICC have been established, there is limited information on the efficacy of therapy targeting this disease.…”

Section: Introductionmentioning

confidence: 99%

WWP1 upregulation predicts poor prognosis and promotes tumor progression by regulating ubiquitination of NDFIP1 in intrahepatic cholangiocarcinoma

Qian

Gao

et al. 2022

Cell Death Discov.

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WW domain-containing E3 ubiquitin protein ligase1 (WWP1) is reported to be upregulated in many types of human cancers; however, its expression and function in intrahepatic cholangiocarcinoma (ICC) remain unknown. Here, in this study we investigated the expression pattern, clinical prognosis, tumor biological functions, and molecular mechanisms of WWP1 in ICC. The expression of WWP1 in patient tissues was detected by western blotting, immunohistochemistry (IHC), and immunofluorescence. CCK-8, colony formation, EdU, transwell, and xenograft models were used to explore the role of WWP1 in the proliferation and metastasis of ICC. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, and immunofluorescence were performed to detect the potential mechanisms. Our study revealed that WWP1 was highly expressed in ICC, and high levels of WWP1 were associated with poor prognosis. Functionally, WWP1 overexpression enhanced the proliferation and metastasis of ICC cells and vice versa. Mechanistically, MYC could be enriched in the promoter region of WWP1 to facilitate its expression. Then, WWP1 targets Nedd4 family interacting protein1 (NDFIP1) and reduces NDFIP1 protein levels via ubiquitination. Downregulation of NDFIP1 in ICC cells rescued the effects of silenced WWP1 expression. WWP1 expression was also negatively correlated with the protein level of NDFIP1 in patient tissues. In conclusion, WWP1 upregulated by MYC promotes the progression of ICC via ubiquitination of NDFIP1, which reveals that WWP1 might be a potential therapeutic target for ICC.

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Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription

Cited by 145 publications

References 39 publications

circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis

circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

WWP1 upregulation predicts poor prognosis and promotes tumor progression by regulating ubiquitination of NDFIP1 in intrahepatic cholangiocarcinoma

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