Circular RNA hsa_circ_0005239 contributes to hepatocellular carcinoma cell migration, invasion, and angiogenesis by targeting the miR‐34a‐5p/PD‐L1 axis

He, Tingting; Huang, Jintao; Liang, Hansi; Zhong, Bin-Yan; Xu, Guili; Zhu, Xiaoli

doi:10.1002/cbin.12049

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…In the field of oncology, He and colleagues observed an upregulation of hsa_circ_0005239 in hepatocellular carcinoma tissues and cell lines. Overexpression of hsa_circ_0005239 could counteract the suppression of the target gene PD-L1 by miR-34a-5p through a ceRNA mechanism, facilitating cellular migration in hepatocellular carcinoma (He et al 2023 ). In the context of neurological injury, research by Yu et al found that circ-003423 is downregulated in an ox-LDL-induced HBMEC-IM cell model of brain vascular endothelial cell damage.…”

Section: Discussionmentioning

confidence: 99%

circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood–brain barrier integrity and cognitive function in uremic encephalopathy

Liu,

Qin,

Zhang

2024

Cell Biol Toxicol

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Uremic encephalopathy (UE) poses a significant challenge in neurology, leading to the need to investigate the involvement of non-coding RNA (ncRNA) in its development. This study employed ncRNA-seq and RNA-seq approaches to identify fundamental ncRNAs, specifically circRNA and miRNA, in the pathogenesis of UE using a mouse model. In vitro and in vivo experiments were conducted to explore the circRNA-PTPN4/miR-301a-3p/FOXO3 axis and its effects on blood–brain barrier (BBB) function and cognitive abilities. The research revealed that circRNA-PTPN4 binds to and inhibits miR-301a-3p, leading to an increase in FOXO3 expression. This upregulation results in alterations in the transcriptional regulation of ZO-1, affecting the permeability of human brain microvascular endothelial cells (HBMECs). The axis also influences the growth, proliferation, and migration of HBMECs. Mice with UE exhibited cognitive deficits, which were reversed by overexpression of circRNA-PTPN4, whereas silencing FOXO3 exacerbated these deficits. Furthermore, the uremic mice showed neuronal loss, inflammation, and dysfunction in the BBB, with the expression of circRNA-PTPN4 demonstrating therapeutic effects. In conclusion, circRNA-PTPN4 plays a role in promoting FOXO3 expression by sequestering miR-301a-3p, ultimately leading to the upregulation of ZO-1 expression and restoration of BBB function in mice with UE. This process contributes to the restoration of cognitive abilities. Graphical Abstract 1. The circRNA-PTPN4/miR-301a-3p/FOXO3 axis is identified as a key regulator of blood–brain barrier integrity and cognitive function in uremic encephalopathy. 2. circRNA-PTPN4 sequestration of miR-301a-3p enhances FOXO3 expression, leading to upregulation of ZO-1 and improved endothelial permeability. 3. Overexpression of circRNA-PTPN4 in uremic mice restores cognitive abilities and reduces neuronal loss and inflammatory infiltration.

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Section: Discussionmentioning

confidence: 99%

circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood–brain barrier integrity and cognitive function in uremic encephalopathy

Liu,

Qin,

Zhang

2024

Cell Biol Toxicol

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“…Has-circ-0005239 promoted migration, invasion, and angiogenesis by controlling PD-L1 expression in HCC. These results revealed that has-circ-0005239 might be a potential therapeutic target for patients with advanced HCC ( 160 ). Exogenous and hepatic stellate cell (HSC) exosome derived circWDR25 promoted the proliferation and invasion of HCC cells through the circWDR25/miR-4474-3p/ALOX15 and EMT axes.…”

Section: Expression Of Pd-l1 In Tumor Cellsmentioning

confidence: 96%

The current status and future of PD-L1 in liver cancer

Hao,

Li,

Deng

et al. 2023

Front. Immunol.

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The application of immunotherapy in tumor, especially immune checkpoint inhibitors (ICIs), has played an important role in the treatment of advanced unresectable liver cancer. However, the efficacy of ICIs varies greatly among different patients, which has aroused people’s attention to the regulatory mechanism of programmed death ligand-1 (PD-L1) in the immune escape of liver cancer. PD-L1 is regulated by multiple levels and signaling pathways in hepatocellular carcinoma (HCC), including gene variation, epigenetic inheritance, transcriptional regulation, post-transcriptional regulation, and post-translational modification. More studies have also found that the high expression of PD-L1 may be the main factor affecting the immunotherapy of liver cancer. However, what is the difference of PD-L1 expressed by different types of cells in the microenvironment of HCC, and which type of cells expressed PD-L1 determines the effect of tumor immunotherapy remains unclear. Therefore, clarifying the regulatory mechanism of PD-L1 in liver cancer can provide more basis for liver cancer immunotherapy and combined immune treatment strategy. In addition to its well-known role in immune regulation, PD-L1 also plays a role in regulating cancer cell proliferation and promoting drug resistance of tumor cells, which will be reviewed in this paper. In addition, we also summarized the natural products and drugs that regulated the expression of PD-L1 in HCC.

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Identification of GNB1 as a downstream effector of the circRNA-0133711/miR-145-5p axis involved in breast cancer proliferation and metastasis

Zou,

Chen,

et al. 2024

Oncologie

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Objectives Despite the involvement of the G protein beta-1 (GNB1) protein in various cancer types, its relationship to breast tumours is presently uncertain. This research focused on the expression of GNB1 in breast cancer and its possible biological ramifications in an effort to explain this confusion. Methods The expression levels of GNB1 in adjacent normal tissues and breast cancer were compared. We next constructed GNB1-overexpressed or -knockdown MDA-MB-231 cell lines in order to clarify GNB1’s function in breast cancer. We used colony-formation assays, CCK-8 assays, xenograft models, and transwell migration/invasion assays to evaluate the effect of GNB1 on tumorigenicity, migration, and invasion. Moreover, we used western blot analysis to investigate the significance of FAK/mTOR signalling in GNB1-regulated tumour stimulatory effects in breast cancer. Finally, we investigated the upstream regulatory signaling of GNB1 using luciferase reporter and functional repair assays. Results When comparing human breast cancer specimens to specimens of normal tissue, we discovered that GNB1 was noticeably overexpressed. This phenotype was also found to be substantially associated with unfavourable clinical outcomes. Functional research findings indicate that elevated expression of GNB1 stimulated the proliferation and metastasis of breast cancer cells. Additionally, we discovered that GNB1 activated the FAK/mTOR signalling cascade by directly inducing the phosphorylation of the FAK protein through specific contacts. According to the results of the RNA pull-down assays and dual-luciferase reporter, we concluded that circRNA-0133711 functions as a competitive endogenous RNA (ceRNA) that sequesters miR-145-5p and thereby relieves its repressive effect on GNB1 expression. Conclusions Collectively, our research findings elucidate the hitherto unexplored important role of the circRNA-0133711/miR-145-5p/GNB1 axis in the formation of breast cancer, and provide a new biomarker for clinical diagnosis and treatment of breast cancer.

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Circular RNA hsa_circ_0005239 contributes to hepatocellular carcinoma cell migration, invasion, and angiogenesis by targeting the miR‐34a‐5p/PD‐L1 axis

Cited by 3 publications

References 43 publications

circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood–brain barrier integrity and cognitive function in uremic encephalopathy

circRNA-PTPN4 mediated regulation of FOXO3 and ZO-1 expression: implications for blood–brain barrier integrity and cognitive function in uremic encephalopathy

The current status and future of PD-L1 in liver cancer

Identification of GNB1 as a downstream effector of the circRNA-0133711/miR-145-5p axis involved in breast cancer proliferation and metastasis

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