<i>MANBA</i>polymorphism was related to increased risk of colorectal cancer in Swedish but not in Chinese populations

Gao, Jingfang; Arbman, Gunnar; He, Lili; Qiao, Fang; Zhang, Zhiyong; Zhao, Zhenze; Rosell, Johan; Sun, Xiao Feng

doi:10.1080/02841860701644052

Cited by 6 publications

(4 citation statements)

References 13 publications

(6 reference statements)

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“…The Venn diagram demonstrated signi cant upregulation of hsa_circRNA_000274 and hsa_circRNA_000708 (circRNA-MANBA) in both datasets (Additional le 1: Figure S1C). A thorough search of the PubMed database yielded literature indicating that MANBA has been implicated in tumor progression (23). Thus, circRNA-MANBA was used for further research.…”

Section: Resultsmentioning

confidence: 99%

Exosomal CircRNA-MANBA Mediates Hepatocellular Carcinoma Sorafenib Resistance via miR-1290/CD109/p-STAT3 Axis

Peng,

Lu,

Nie

et al. 2023

Preprint

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Background Sorafenib remains the cornerstone chemotherapeutic treatment for patients with late-stage hepatocellular carcinoma (HCC). Unfortunately, resistance to this drug in the context of the disease is frequent, and the underlying mechanisms remain unclear. In this regard, exosome-contained noncoding RNAs (ncRNAs) have been proven to participate in various diseases. Here, we aimed to identify the exosomal circular RNA (circRNA)-mediated mechanism by which sorafenib resistance develops in HCC. Methods Differential expression of exosomal circRNAs from parental and sorafenib-resistant HCC cells were examined by microarray. Cell viability, colony formation, apoptosis, and TUNEL assays were performed to determine HCC drug resistance following siRNA treatment. Exosomes from sorafenib-resistant HCC cells were harvested and incubated with parental cells. Bioinformatics analysis, quantitative real-time PCR, immunohistochemistry, and Western blot, were performed determine the downstream targets of circRNA. Results CircRNA-MANBA was overexpressed in sorafenib-resistant cell lines, and present in high concentrations in exosomes secreted by resistant cells. Inhibition of circRNA-MANBA significantly increased the cell-killing effect of sorafenib. Analysis of tissue samples from sorafenib-treated HCC patients revealed an association between circRNA-MANBA and poor overall/disease-free survival. The sensitivity of parental HCC was substantially impaired after co-culture with exosomes from resistant cells, and transfection of siRNA targeting circRNA-MANBA could partially reverse the attenuation of sensitization to sorafenib. Mechanically, circRNA-MANBA acted as an “miRNA sponge” to absorb miR-1290, preventing it from interacting with CD109, and therefore upregulating STAT3 phosphorylation (S727). Targeting miR-1290 activation with an inhibitor or mimic could strengthen or reverse the effect of si-circRNA-MANBA on drug sensitivity, respectively. Conclusions Our findings demonstrate the unique role of exosomal circRNA-MANBA in the regulation and transfer of resistance to sorafenib and propose a potential strategy to overcome drug resistance in progressive HCC.

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Section: Resultsmentioning

confidence: 99%

Exosomal CircRNA-MANBA Mediates Hepatocellular Carcinoma Sorafenib Resistance via miR-1290/CD109/p-STAT3 Axis

Peng,

Lu,

Nie

et al. 2023

Preprint

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“…A gene deficiency may cause β -mannoside storage disease, which can be accompanied by a wide range of neurological symptoms ( 53 ). In some studies, the role of MANBA in cancer has been reported, such as being involved in the occurrence and metastasis of colorectal cancer and human esophageal squamous cell carcinoma ( 54 , 55 ). Wielgat ( 56 ) has discovered that the glycosidase activity is positively correlated with the malignancy of glioma, which is consistent with our findings.…”

Section: Discussionmentioning

confidence: 99%

Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics

Xing,

Cai,

Lin

et al. 2024

Front. Immunol.

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BackgroundGlioblastoma (GBM), a prevalent malignant neoplasm within the neuro-oncological domain, has been a subject of considerable scrutiny. Macrophages, serving as the principal immunological constituents, profoundly infiltrate the microenvironment of GBM. However, investigations elucidating the intricate immunological mechanisms governing macrophage involvement in GBM at the single-cell level remain notably limited.MethodsWe conducted a comprehensive investigation employing single-cell analysis, aiming to redefine the intricate cellular landscape within both the core and peripheral regions of GBM tumors. Our analytical focus extended to the profound study of macrophages, elucidating their roles within the context of oxidative stress, intercellular information exchange, and cellular trajectories concerning GBM and its assorted subpopulations. We pursued the identification of GBM prognostic genes intricately associated with macrophages. Utilizing experimental research to investigate the relevance of MANBA in the context of GBM.ResultsOur investigations have illuminated the central role of macrophages in the intricate interplay among various subpopulations within the GBM microenvironment. Notably, we observed a pronounced intensity of oxidative stress responses within macrophages when compared to their GBM counterparts in other subpopulations. Moreover, macrophages orchestrated intricate cellular communication networks, facilitated by the SPP1-CD44 axis, both internally and with neighboring subpopulations. These findings collectively suggest the potential for macrophage polarization from an M1 to an M2 phenotype, contributing to immune suppression within the tumor microenvironment. Furthermore, our exploration unearthed GBM prognostic genes closely associated with macrophages, most notably MANBA and TCF12. Remarkably, MANBA appears to participate in the modulation of neuroimmune functionality by exerting inhibitory effects on M1-polarized macrophages, thereby fostering tumor progression. To bolster these assertions, experimental validations unequivocally affirmed the promotional impact of MANBA on GBM, elucidated through its capacity to curb cell proliferation, invasiveness, and metastatic potential.ConclusionThese revelations represent a pivotal step towards unraveling the intricate immunological mechanisms governing the interactions between macrophages and diverse subpopulations within the GBM milieu. Furthermore, they lay the foundation for the development of an innovative GBM prognostic model, with MANBA at its epicenter, and underscore the potential for novel immunotherapeutic targets in the ongoing pursuit of enhanced treatment modalities for this formidable malignancy.

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“…Mannosidase represents the concluding exoglycosidase acting in the N-linked oligosaccharide degradation pathway, affecting the terminal breakdown of glycoprotein moieties [ 18 ]. In recent years, MANBA, a gene encoding β-mannosidase, has been associated with cancer [ 19 ]. Studies have found that Polymorphisms increase the risk of colorectal cancer in swine.…”

Section: Discussionmentioning

confidence: 99%

A novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in oral squamous cell carcinoma

Liu,

Xu,

Liu

et al. 2024

Heliyon

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MANBApolymorphism was related to increased risk of colorectal cancer in Swedish but not in Chinese populations

Cited by 6 publications

References 13 publications

Exosomal CircRNA-MANBA Mediates Hepatocellular Carcinoma Sorafenib Resistance via miR-1290/CD109/p-STAT3 Axis

Exosomal CircRNA-MANBA Mediates Hepatocellular Carcinoma Sorafenib Resistance via miR-1290/CD109/p-STAT3 Axis

Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics

A novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in oral squamous cell carcinoma

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