MicroRNA miR-29a Inhibits Colon Cancer Progression by Downregulating B7-H3 Expression: Potential Molecular Targets for Colon Cancer Therapy

Wang, Jin; Chen, Xiaojuan; Xie, Chen; Sun, Mingbing; Hu, Chenrui; Zhang, Zhe; Luan, Lipeng; Zhou, Jin; Zhou, Jian; Zhu, Xinguo; Ouyang, Jun; Dong, Xiaoqiang; Li, Dechun; Zhang, Jianglei; Zhao, Xin

doi:10.1007/s12033-021-00348-1

Cited by 16 publications

(12 citation statements)

References 36 publications

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“…For instance, Yan et al demonstrated that hsa-miR-125a was upregulated in human colon cancer cells (SW480) [ 57 ]. Wang et al [ 58 ] discovered that miR-29a inhibited the evolution of colon cancer by down-regulating the B7-H3 expression.…”

Section: Resultsmentioning

confidence: 99%

Predicting miRNA-disease associations based on graph attention network with multi-source information

Fang

Zhang

et al. 2022

BMC Bioinformatics

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Background There is a growing body of evidence from biological experiments suggesting that microRNAs (miRNAs) play a significant regulatory role in both diverse cellular activities and pathological processes. Exploring miRNA-disease associations not only can decipher pathogenic mechanisms but also provide treatment solutions for diseases. As it is inefficient to identify undiscovered relationships between diseases and miRNAs using biotechnology, an explosion of computational methods have been advanced. However, the prediction accuracy of existing models is hampered by the sparsity of known association network and single-category feature, which is hard to model the complicated relationships between diseases and miRNAs. Results In this study, we advance a new computational framework (GATMDA) to discover unknown miRNA-disease associations based on graph attention network with multi-source information, which effectively fuses linear and non-linear features. In our method, the linear features of diseases and miRNAs are constructed by disease-lncRNA correlation profiles and miRNA-lncRNA correlation profiles, respectively. Then, the graph attention network is employed to extract the non-linear features of diseases and miRNAs by aggregating information of each neighbor with different weights. Finally, the random forest algorithm is applied to infer the disease-miRNA correlation pairs through fusing linear and non-linear features of diseases and miRNAs. As a result, GATMDA achieves impressive performance: an average AUC of 0.9566 with five-fold cross validation, which is superior to other previous models. In addition, case studies conducted on breast cancer, colon cancer and lymphoma indicate that 50, 50 and 48 out of the top fifty prioritized candidates are verified by biological experiments. Conclusions The extensive experimental results justify the accuracy and utility of GATMDA and we could anticipate that it may regard as a utility tool for identifying unobserved disease-miRNA relationships.

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Section: Resultsmentioning

confidence: 99%

Predicting miRNA-disease associations based on graph attention network with multi-source information

Fang

Zhang

et al. 2022

BMC Bioinformatics

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“…Additionally, B7-H3 protein expression correlated contrariwise with miR-29 levels in these tumors [22]. Results of different studies confirmed that miR-29 miRNAs downregulate B7-H3 expression by targeting B7-H3 3 UTR, which contains a miR-29 binding site [22,59,60]. Finally, Cheung et al demonstrated the miR-29 downregulation in NB metastatic to the CNS compared with primary tumors.…”

Section: Regulation Of B7-h3 Expression In Extracranial Pstsmentioning

confidence: 87%

“…Abnormal miRNA expression in cancer may be either detected as downor upregulation, meaning various families of these molecules could act either as oncogenes or as tumor suppressors [53]. Forasmuch as the abovementioned roles of miRNAs as regulators of cancer formation and metastasis, different studies have investigated the relationship between miRNA and B7-H3, as a carcinogenesis-associated protein, primarily expressed only in tumor tissues [22,23,59,60]. It has been noticed that a specific member of the miRNA family, miR-29a, was vastly expressed in normal tissues, but downregulated in different solid tumors, including sarcomas, NB, and brain tumors.…”

Section: Regulation Of B7-h3 Expression In Extracranial Pstsmentioning

confidence: 99%

Targeting B7-H3—A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment

Rasic

Jeremic

et al. 2023

Molecules

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Recent scientific data recognize the B7-H3 checkpoint molecule as a potential target for immunotherapy of pediatric solid tumors (PSTs). B7-H3 is highly expressed in extracranial PSTs such as neuroblastoma, rhabdomyosarcoma, nephroblastoma, osteosarcoma, and Ewing sarcoma, whereas its expression is absent or very low in normal tissues and organs. The influence of B7-H3 on the biological behavior of malignant solid neoplasms of childhood is expressed through different molecular mechanisms, including stimulation of immune evasion and tumor invasion, and cell-cycle disruption. It has been shown that B7-H3 knockdown decreased tumor cell proliferation and migration, suppressed tumor growth, and enhanced anti-tumor immune response in some pediatric solid cancers. Antibody-drug conjugates targeting B7-H3 exhibited profound anti-tumor effects against preclinical models of pediatric solid malignancies. Moreover, B7-H3-targeting chimeric antigen receptor (CAR)-T cells demonstrated significant in vivo activity against different xenograft models of neuroblastoma, Ewing sarcoma, and osteosarcoma. Finally, clinical studies demonstrated the potent anti-tumor activity of B7-H3-targeting antibody-radioimmunoconjugates in metastatic neuroblastoma. This review summarizes the established data from various PST-related studies, including in vitro, in vivo, and clinical research, and explains all the benefits and potential obstacles of targeting B7-H3 by novel immunotherapeutic agents designed to treat malignant extracranial solid tumors of childhood.

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“…Based on the above, the substance in exosomes such as miR-29a-3p may have different significance and effects. Reports have shown that the detection of miR-29a-3p in glioma can be used as a malignant marker after making a definite diagnosis (23)(24)(25), then, if possible, the glioma can be staged according to the expression of miR-29a-3p and clinical data. As miR-29a-3p expressed in peripheral blood can be used as a biomarker for the preliminary diagnosis of disease, and may be used as an early marker for disease screening, this highlights the significance of detecting it in peripheral blood (26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway

2023

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Exosomes secreted by glioma cells can carry a number of bioactive molecules. As the most abundant noncoding RNA in exosomes, microRNAs (miRNAs) are involved in signaling between tumor cells in a number of ways. In addition, hypoxia is an important feature of the microenvironment of most tumors. The present study investigated the effect of miR-29a-3p in glioma exosomes on the proliferation and apoptosis levels of U251 glioma cells under hypoxia. Qualitative PCR results showed that the expression level of miR-29a-3p in plasma exosomes of glioma patients was lower than that of normal subjects. By conducting hypoxia experiments in vitro on U251 glioma cells, it was found that the expression level of miR-29a-3p decreased following hypoxia, while overexpression of miR-29a-3p significantly decreased the proliferation of U251 glioma cells and promoted apoptosis by inhibiting the expression of the antiapoptotic marker Bcl-2 and increasing the expression of the proapoptotic marker Bax The potential targets of miR-29a-3p were predicted by online tools and validated by a dual-luciferase gene reporter assay. miR-29a-3p was found to target and regulate PI3K, which in turn inhibited the activity of the PI3K-AKT pathway, thereby reducing the expression of hypoxia inducible factor (HIF)-1α protein. Furthermore, the effects of miR-29a-3p on proliferation and apoptosis in glioma cells in those processes could be reversed by the PI3K-AKT agonist Recilisib. In addition, the inhibitory effect of miR-29a-3p on the PI3K/AKT/HIF-1α regulatory axis could cause a decrease in the expression levels of pyruvate dehydrogenase kinase-1 and pyruvate dehydrogenase kinase-2 and eventually lead to a reduction in glycolysis in U251 glioma cells. Similarly, Recilisib slowed the inhibitory effect of miR-29a-3p on glycolysis and glycolysis-related molecules. The results of this study tentatively confirm that miR-29a-3p carried by exosomes can be used as a novel diagnostic marker and a potential inhibitory molecule for glioma cells, providing a new theoretical and experimental basis for the precise clinical treatment of glioma.

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MicroRNA miR-29a Inhibits Colon Cancer Progression by Downregulating B7-H3 Expression: Potential Molecular Targets for Colon Cancer Therapy

Cited by 16 publications

References 36 publications

Predicting miRNA-disease associations based on graph attention network with multi-source information

Predicting miRNA-disease associations based on graph attention network with multi-source information

Targeting B7-H3—A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment

Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway

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