ACTR3 promotes cell migration and invasion by inducing epithelial mesenchymal transition in pancreatic ductal adenocarcinoma

Hu, Hao; Zhang, Shuo; Xiong, Shuming; Hu, Benshun; He, Youzhao; Gu, Yuanlong

doi:10.21037/jgo-21-609

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…At the same time, preincubation with the Notch signaling inhibitor (LY411575) abolished the effects on the Notch signal but did not affect the expression of both LOX and LOXL1 (Figure 5 C). Meanwhile, we also found the crosstalk of LOX and LOXL1 amplified the marker gene expression of HSC activation ( Col1a1 and Acta2 ), proliferation ( Mki67 and Pcna ), migration ( Arhgef4 and Actr3 ), 21 , 22 and contraction ( Rhoa ), 23 which was counteracted by LY411575 pretreatment (Figure 5 D). To sum up, synergistically elevated LOX and LOXL1 and their crosstalk in HSCs during liver fibrogenesis enhanced the stabilities of LOX and LOXL1, specifically prolonging the stimulation on their downstream Notch signal.…”

Section: Resultsmentioning

confidence: 86%

Crosstalk of lysyl oxidase-like 1 and lysyl oxidase prolongs their half-lives and regulates liver fibrosis through Notch signal

Zhang,

Yang,

Zhang

et al. 2024

Hepatology Communications

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Background: Lysyl oxidase (LOX) family members (LOX and LOXL1 to 4) are crucial copper-dependent enzymes responsible for cross-linking collagen and elastin. Previous studies have revealed that LOX and LOXL1 are the most dramatically dysregulated LOX isoforms during liver fibrosis. However, the crosstalk between them and the underlying mechanisms involved in the profibrotic behaviors of HSCs, as well as the progression of liver fibrosis, remain unclear. Methods: pCol9GFP-HS4,5Tg mice, Loxl1 fl/fl Gfap Cre mice, human HSC line, and primary HSCs were enrolled to study the dysregulation pattern, profibrotic roles, and the potential mechanisms of LOX and LOXL1 interaction involved in the myofibroblast-like transition of HSCs and liver fibrogenesis. Results: LOX and LOXL1 were synergistically upregulated during liver fibrogenesis, irrespective of etiology, together orchestrating the profibrotic behaviors of HSCs. LOX and LOXL1 coregulated in HSCs, whereas LOXL1 dominated in the coregulation loop. Interestingly, the interaction between LOXL1 and LOX prolonged their half-lives, specifically enhancing the Notch signal-mediated myofibroblast-like transition of HSCs. Selective disruption of Loxl1 in Gfap + HSCs deactivated the Notch signal, inhibited HSC activation, and relieved carbon tetrachloride-induced liver fibrosis. Conclusions: Our current study confirmed the synergistic roles and the underlying mechanisms of LOXL1 and LOX crosstalk in the profibrotic behaviors of HSCs and liver fibrosis progression, providing experimental evidence for further clear mechanism-based anti-LOXL1 strategy development in the therapy of liver fibrosis.

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Section: Resultsmentioning

confidence: 86%

Crosstalk of lysyl oxidase-like 1 and lysyl oxidase prolongs their half-lives and regulates liver fibrosis through Notch signal

Zhang,

Yang,

Zhang

et al. 2024

Hepatology Communications

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“…Actin-related protein 3 (ACTR3) and ACTR2 are important subunits of ARP2/3 complex, the protein they encode are known to be the major constituents of the ARP2/3 complex. ARP2/3 complex has been proved to be involved in the regulation of cell motility and epithelial mesenchymal transition (EMT) process, and is closely associated with cancer development of gastric cancer, squamous cell carcinoma, and colorectal cancer [43,44]. Tyrosine 3 monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), belonging to the 14-3-3 protein family, is a central hub protein involved in many signal transduction pathways and plays a key role in tumor progression, and participate in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration/invasion in multiple types of cancers [45].…”

Section: Discussionmentioning

confidence: 99%

Sequencing and validation of exosomal miRNAs panel as novel plasma biomarkers for early diagnosis and prognosis prediction in laryngeal cancer

Zhang

Chen

Huang

et al. 2023

Preprint

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Purpose Plasma exosomal miRNAs are important biomarkers for body fluid biopsy. The purpose of this study was to screen and construct plasma exosomal miRNAs panel as biomarkers for diagnosis and prognosis in laryngeal squamous cell carcinoma (LSCC). Methods Plasma exosomal miRNAs from 6 LSCC patients with three typical anatomical sites and 3 normal controls (NC) were analyzed by next-generation sequencing. The obtained aberrant expression profile of exosomal miRNAs were compared with the online databases of LSCC to construct and verify the diagnostic and prognostic panel by machine learning. Also, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the diagnostic efficacy of the screened miRNAs in an independent clinical cohort. Results A plasma exosomal miRNAs panel (consisting of hsa-miR-139-3p, hsa-miR-486-5p, hsa-miR-944, hsa-miR-320b and hsa-miR-455-5p) was successfully constructed for early diagnosis and prognosis of LSCC, and showed good predictive potential with an AUC of 0.782, 1.000, 0.716, and 0.875 by artificial neural network (ANN) panel in the independent datasets. This panel was further validation in an independent cohort consisting of 84 clinical cases (48 LSCC and 36 NC). In the validation cohort, the AUC of 5 individual miRNAs ranged from 0.721 to 0.837. The accuracy was further increased by the logistic model, which further increased the AUC to 0.959 by adjusting for the number of miRNAs. The mRNA-miRNA regulatory network and immune function analysis revealed the possible underlying pathogenesis of LSCC. Conclusions Exosomal miRNAs panel can be promising plasma biomarkers for predicting early diagnosis and prognosis in LSCC.

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“…We will further investigate the expression levels of miR-128-3p and ZEB1 and their correlation in clinical samples in future studies. Apart from ZEB1, there are too many genes such as ACTR 3 and FGFR2c ( Hu et al., 2021 ; Ranieri et al., 2021 ) that play regulatory roles in EMT in PC to list. These are not the downstream targets of miR-128-3p and are associated with other regulatory signaling pathways that fall outside of this study.…”

Section: Discussionmentioning

confidence: 99%

Functional mechanism of hsa-miR-128-3p in epithelial-mesenchymal transition of pancreatic cancer cells via ZEB1 regulation

Zheng

Han

Wang

et al. 2022

PeerJ

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Pancreatic cancer (PC) often correlates with high mortality due to late diagnosis, rapid metastasis, and resistance to chemotherapy. miR-128-3p has been validated as a tumor suppressor in PC. This study explored the functional mechanism of miR-128-3p in epithelial-mesenchymal transition (EMT) of PC cells. Four PC cancer cell lines with different degrees of malignancy and normal pancreatic cells were selected to detect expressions of hsa-miR-128-3p and ZEB1 by RT-qPCR and Western blot. miR-128-3p mimic or si-ZEB1 was delivered into PANC-1 cells and miR-128-3p inhibitor or oe-ZEB1 was delivered into AsPC-1 cells. Expressions of epithelial and mesenchymal markers were analyzed by Western blot and cell fluorescence staining. The binding relationship between miR-128-3p and ZEB1 was examined by bioinformatics analysis and dual-luciferase assay, and verified by RT-qPCR and Western blot. PC cell invasion and migration were assessed by Transwell assays. Generally, hsa-miR-128-3p was poorly-expressed in PC cells. However, it was relatively more expressed in AsPC-1 cells with epithelial phenotypes relative to PANC-1 cells with mesenchymal phenotype, whereas ZEB1 expression showed opposite tendencies. PANC-1 cells transfected with miR-128-3p mimic or si-ZEB1 showed upregulated E-cadherin and downregulated N-cadherin, and transformed from mesenchymal phenotypes to epithelial phenotypes, with decreased invasion and migration, while opposite results occurred in AsPC-1 cells transfected with miR-128-3p inhibitor or oe-ZEB1. miR-128-3p targeted ZEB1. oe-ZEB1 antagonized the inhibition of miR-128-3p mimic on PANC-1 cell EMT, invasion, and migration, while si-ZEB1 reversed the facilitation of miR-128-3p inhibitor in AsPC-1 cells. In conclusion, miR-128-3p inhibited PC cell EMT, invasion, and migration by targeting ZEB1.

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ACTR3 promotes cell migration and invasion by inducing epithelial mesenchymal transition in pancreatic ductal adenocarcinoma

Cited by 7 publications

References 29 publications

Crosstalk of lysyl oxidase-like 1 and lysyl oxidase prolongs their half-lives and regulates liver fibrosis through Notch signal

Crosstalk of lysyl oxidase-like 1 and lysyl oxidase prolongs their half-lives and regulates liver fibrosis through Notch signal

Sequencing and validation of exosomal miRNAs panel as novel plasma biomarkers for early diagnosis and prognosis prediction in laryngeal cancer

Functional mechanism of hsa-miR-128-3p in epithelial-mesenchymal transition of pancreatic cancer cells via ZEB1 regulation

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