The Canonical WNT Pathway in Gastric Carcinoma

Oliveira, Lauro Augusto de; Oshima, Celina Tizuko Fujiyama; Soffner, Pedro Augusto; Silva, Marcelo de Souza; Lins, Rodrigo Rego; Malinverni, Andréa Cristina de Moraes; Waisberg, Jaques

doi:10.1590/0102-672020180001e1414

Cited by 11 publications

(11 citation statements)

References 33 publications

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“…Next, WNT2, a secreted glycoprotein, was predicted to be a potential target gene of miR-30a-3p by bioinformatics analysis. It has been reported that WNT2 can promote the development of tumors [ 42 – 44 ], and the WNT2/β-Catenin signaling pathway is related to the malignant biological functions of GC [ 45 – 47 ]. This protein drew our attention.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway

Cao

Zhang

et al. 2021

J Exp Clin Cancer Res

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Background Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism). Methods Through RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2′-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization. Results CircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo. CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7. Conclusions CircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway

Cao

Zhang

et al. 2021

J Exp Clin Cancer Res

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“…Recently, immunohistochemical analysis was performed to evaluate the expression of FZD5, CK1, Wnt5a, axin, GSK3β, ubiquitin, c-Myc , and cyclin D1—the results obtained are still unclear. Nonetheless, higher expression of components of the canonical Wnt pathway has been identified in samples of human gastric carcinomas [183].…”

Section: Wnt Signaling In Cancermentioning

confidence: 99%

Wnt Signaling in the Regulation of Immune Cell and Cancer Therapeutics

Haseeb

Pirzada

Ain

et al. 2019

Cells

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Wnt signaling is one of the important pathways to play a major role in various biological processes, such as embryonic stem-cell development, tissue regeneration, cell differentiation, and immune cell regulation. Recent studies suggest that Wnt signaling performs an essential function in immune cell modulation and counteracts various disorders. Nonetheless, the emerging role and mechanism of action of this signaling cascade in immune cell regulation, as well as its involvement in various cancers, remain debatable. The Wnt signaling in immune cells is very diverse, e.g., the tolerogenic role of dendritic cells, the development of natural killer cells, thymopoiesis of T cells, B-cell-driven initiation of T-cells, and macrophage actions in tissue repair, regeneration, and fibrosis. The purpose of this review is to highlight the current therapeutic targets in (and the prospects of) Wnt signaling, as well as the potential suitability of available modulators for the development of cancer immunotherapies. Although there are several Wnt inhibitors relevant to cancer, it would be worthwhile to extend this approach to immune cells.

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“…Next, WNT2, a secreted glycoprotein, was predicted to be a potential target gene of miR-30a-3p by bioinformatics analysis. It has been reported that WNT2 can promote the development of tumors [42][43][44], and the WNT2/β-Catenin signaling pathway is related to the malignant biological functions of GC [45][46][47]. This protein drew our attention.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-Catenin pathway

Cao

Zhang

et al. 2020

Preprint

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Background : Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism). Methods: Through RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2’-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization. Results: CircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo . CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7. Conclusions: CircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.

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The Canonical WNT Pathway in Gastric Carcinoma

Cited by 11 publications

References 33 publications

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway

Wnt Signaling in the Regulation of Immune Cell and Cancer Therapeutics

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-Catenin pathway

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