A tumor-suppressive circular RNA mediates uncanonical integrin degradation by the proteasome in liver cancer

Shi, Liang; Liu, Boqiang; Shen, Dan‐Dan; Yan, Peijian; Zhang, Yanan; Tian, Yuanshi; Hou, Lidan; Jiang, Guangyi; Zhu, Yinxin; Liang, Yuelong; Liang, Xiao; Shen, Bo; Yu, Hong; Zhang, Yan; Wang, Yifan; Guo, Xing; Cai, Xiujun

doi:10.1126/sciadv.abe5043

Cited by 55 publications

(66 citation statements)

References 64 publications

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“…After Co-IP with YAP antibody, protein samples were washed out and prepared for LC-MS/MS analysis. The raw data from LC-MS/MS analysis was conducted for database search and quantitative analysis (MaxQuant, version 1.5.6.0) [28]. The Gene Ontology (GO) functional analysis was performed for the differential expression of proteins.…”

Section: Mem-per™ Plus Membrane Protein Extraction Kit and Ne-per™ Nuclear And Cytoplasmicmentioning

confidence: 99%

Fluid shear stress activates YAP to promote epithelial–mesenchymal transition in hepatocellular carcinoma

et al. 2021

Molecular Oncology

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Epithelial-mesenchymal transition (EMT) mediated by fluid shear stress (FSS) in the tumor microenvironment plays an important role in driving metastasis of the malignant tumor. As a mechanotransducer, Yes-associated protein (YAP) is known to translocate into the nucleus to initiate transcription of genes involved in cell proliferation upon extracellular biophysical stimuli.Here, we showed that FSS facilitated cytoskeleton rearrangement in hepatocellular carcinoma cells, which led to the release of YAP from its binding partner, integrin β subunit, in the cytomembrane. Moreover, we found that upregulation of GEF-H1, a microtubule-associated Rho guanine nucleotide exchange factor (GEF), is a critical step in the FSS-induced translocation of YAP. Nuclear YAP activated the expression of the EMT-regulating transcription factor SNAI1, but suppressed the expression of N6-methyladenosine (m 6 A) modulators; together, this promoted the expression of EMT-related genes. We also observed that FSS-treated HepG2 cells showed markedly increased tumorigenesis and metastasis in vivo. Collectively, our findings unravel the underlying molecular processes by which FSS induces translocation of YAP from the cytomembrane to the nucleus, contributes to EMT and enhances metastasis in hepatocellular carcinoma.

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Section: Mem-per™ Plus Membrane Protein Extraction Kit and Ne-per™ Nuclear And Cytoplasmicmentioning

confidence: 99%

Fluid shear stress activates YAP to promote epithelial–mesenchymal transition in hepatocellular carcinoma

et al. 2021

Molecular Oncology

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“…These sequencing and bioinformatics analysis statistics demonstrate the possible involvement of circRNAs in HCC tumorigenesis and development. Many studies have reported that circRNAs play an important role in HCC, although their specific functions and internal mechanisms are still under investigation [ 36 , 37 , 39 – 60 ] (Table 1 ).…”

Section: Circrnas Profile In Hccmentioning

confidence: 99%

“…Many studies have reported that circRNAs play an important role in HCC, although their specific functions and internal mechanisms are still under investigation [ 36 , 37 , 39 – 60 ] (Table 1 ).…”

Section: Circrnas Profile In Hccmentioning

confidence: 99%

“…In contrast, circADD3 was suggested to strengthen the interaction between CDK1 and EZH2 to facilitate EZH2 ubiquitination and subsequent degradation, indicating that circADD3 functions as a protein scaffold in CDK1-mediated EZH2 ubiquitination and ultimately restrains HCC metastasis [ 55 ]. Additionally, our group reported that circPABPC1 could exert a critical tumor-suppressive function by directly feeding ITGβ1, a classic membrane protein, to the proteasome for ubiquitin-independent degradation in HCC [ 60 ]. This unexpected finding should have a significant impact on our understanding of substrate recognition and protein degradation by the proteasome.…”

Section: Mechanisms Of Circrnas In Hccmentioning

confidence: 99%

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Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer

Shen

Liu

et al. 2021

J Hematol Oncol

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Background Hepatocellular carcinoma (HCC) is one of the most common malignancies globally. Despite aggressive and multimodal treatment regimens, the overall survival of HCC patients remains poor. Main Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with covalently closed structures and tissue- or organ-specific expression patterns in eukaryotes. They are highly stable and have important biological functions, including acting as microRNA sponges, protein scaffolds, transcription regulators, translation templates and interacting with RNA-binding protein. Recent advances have indicated that circRNAs present abnormal expression in HCC tissues and that their dysregulation contributes to HCC initiation and progression. Furthermore, researchers have revealed that some circRNAs might serve as diagnostic biomarkers or drug targets in clinical settings. In this review, we systematically evaluate the characteristics, biogenesis, mechanisms and functions of circRNAs in HCC and further discuss the current shortcomings and potential directions of prospective studies on liver cancer-related circRNAs. Conclusion CircRNAs are a novel class of ncRNAs that play a significant role in HCC initiation and progression, but their internal mechanisms and clinical applications need further investigation.

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“…As a tumor suppressor in HCC, circPABPC1 physically links ITGB1 (b1 integrin) to proteasomes for degradation in a ubiquitin-independent manner, thereby inhibiting the adhesion and migration of cells. Therefore, circPABPC1 might be a potential prognostic and therapeutic target for HCC (127).…”

Section: Circrnas As Diagnostic and Prognostic Biomarkers For Hccmentioning

confidence: 99%

Circular RNAs in Hepatocellular Carcinoma: Emerging Functions to Clinical Significances

Zhang

Wang

2021

Front. Oncol.

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Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and carries high morbidity and mortality. Diagnosing HCC at an early stage is challenging. Therefore, finding new, highly sensitive and specific diagnostic biomarkers for the diagnosis and prognosis of HCC patients is extremely important. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed loop structures. They are characterized by remarkable stability, long half-life, abundance and evolutionary conservation. Recent studies have shown that many circRNAs are expressed aberrantly in HCC tissues and have important regulatory roles during the development and progression of HCC. Hence, circRNAs are promising biomarkers for the diagnosis and prognosis of HCC. This review: (i) summarizes the biogenesis, categories, and functions of circRNAs; (ii) focuses on current progress of dysregulated expression of circRNAs in HCC with regard to regulation of the tumor hallmarks, “stemness” of cancer cells, and immunotherapy; (iii) highlights circRNAs as potential biomarkers and therapeutic targets for HCC; and (iv) discusses some of the challenges, questions and future perspectives of circRNAs research in HCC.

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A tumor-suppressive circular RNA mediates uncanonical integrin degradation by the proteasome in liver cancer

Cited by 55 publications

References 64 publications

Fluid shear stress activates YAP to promote epithelial–mesenchymal transition in hepatocellular carcinoma

Fluid shear stress activates YAP to promote epithelial–mesenchymal transition in hepatocellular carcinoma

Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer

Circular RNAs in Hepatocellular Carcinoma: Emerging Functions to Clinical Significances

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