Hsa_circ_0049396 inhibited oral squamous cell carcinoma progression by regulating the miR-663b/ENDOU axis

Lou, Ying; Ren, Liuyang; Wang, Lu

doi:10.1016/j.ygeno.2022.110553

Cited by 6 publications

(1 citation statement)

References 23 publications

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“…Human EndoU (hEndoU) was first identified as human placental protein 11 (PP11) due to its prevalence in the placenta [17,18]. It is also now recognized as a biomarker in various cancers, including squamous cell carcinomas, ovarian adenocarcinomas, non-trophoblastic tumors and breast cancers [19,20,21,22,23,24]. In human cells, EndoU has been proposed to be involved in RNA cleavage, ribonucleoprotein particle removal, and endoplasmic reticulum network organization [25,26].…”

Section: Introductionmentioning

confidence: 99%

Molecular Basis for the Calcium-Dependent Activation of the Ribonuclease EndoU

Malard,

Dias,

Baudy

et al. 2024

Preprint

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Ribonucleases (RNases) are ubiquitous enzymes that process or degrade RNA, essential for cellular functions and immune responses. The EndoU-like superfamily includes endoribonucleases conserved across bacteria, eukaryotes, and certain viruses, with an ancient evolutionary link to the ribonuclease A-like superfamily. Both bacterial EndoU and animal RNase A share a similar fold and function independently of cofactors. In contrast, the eukaryotic EndoU catalytic domain requires divalent metal ions for catalysis, possibly due to an N-terminal extension near the catalytic core. In this study, we used biophysical and computational techniques along with in vitro assays to investigate the calcium-dependent activation of human EndoU. We determined the crystal structure of EndoU bound to calcium and found that calcium binding remote from the catalytic triad triggers water-mediated intramolecular signaling and structural changes, activating the enzyme through allostery. Calcium-binding involves residues from both the catalytic core and the N-terminal extension, indicating that the N-terminal extension interacts with the catalytic core to modulate activity in response to calcium. Our findings suggest that similar mechanisms may be present across all eukaryotic EndoUs, highlighting a unique evolutionary adaptation that connects endoribonuclease activity to cellular signaling in eukaryotes.

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Section: Introductionmentioning

confidence: 99%

Molecular Basis for the Calcium-Dependent Activation of the Ribonuclease EndoU

Malard,

Dias,

Baudy

et al. 2024

Preprint

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Hypoxia combined with radiation reverses migration and invasion of head and neck squamous cell carcinoma by remodeling extracellular vesicle‐mediated transfer of miR‐23b‐5p from cancer‐associated fibroblasts

He,

Xie,

Zhang

et al. 2024

Malignancy Spectrum

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BackgroundCancer‐associated fibroblasts (CAFs), the main matrix components in the tumor microenvironment (TME), play a crucial role in tumor progression. Extracellular vesicles (EVs) as main mediators in intercellular communication can be regulated by hypoxia or radiation.MethodsCAFs were extracted from head and neck squamous cell carcinoma (HNSCC) tissues and CAF‐derived EVs were collected by ultracentrifugation. Bioinformatics analysis determined the role of poly (U)‐specific endonuclease (ENDOU) on HNSCC progression and confirmed that ENDOU inhibited HNSCC progression by overexpressing ENDOU in HNSCC. Dual‐luciferase activity report assay confirmed that miR‐23b‐5p was involved in the regulation of ENDOU expression. The migration and invasion of HNSCC cells were verified by transwell assay. Furthermore, tumor‐bearing mouse models were used to demonstrate the potential of EVs loaded with miR‐23b‐5p in HNSCC to promote tumor progression.ResultsOur results showed that ENDOU was downregulated in HNSCC and inhibited HNSCC migration and invasion. Hypoxia and radiotherapy reversed CAF‐derived EVs to promote migration and invasion of HNSCC. Mechanically, hypoxia and radiation downregulated miR‐23b‐5p in CAF‐derived EVs and then restored ENDOU expression in HNSCC. Finally, CAF‐derived EVs carrying miR‐23b‐5p promoted the progression of HNSCC cells in vivo by regulating ENDOU expression.ConclusionThis study demonstrated that hypoxia combined with radiation reverses the promoting effect of CAFs on HNSCC migration and invasion by reducing the delivery of miR‐23b‐5p by CAF‐derived EVs to decrease the inhibitory effect of ENDOU expression in HNSCC. The results provide a new perspective for better understanding the role of stromal components in TME in tumor regulation. Furthermore, the results provide a strong basis for the possibility of ENDOU as a biomarker for HNSCC.

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