MTH1 Inhibitor TH287 Suppresses Gastric Cancer Development Through the Regulation of PI3K/AKT Signaling

Zhan, Dankai; Zhang, Xinxin; Li, Jiahui; Ding, Xiaojiao; Cui, Yan; Jia, Jianguang

doi:10.1089/cbr.2019.3031

Cited by 9 publications

(11 citation statements)

References 39 publications

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“…Hsa_circ_0010882 also activates PI3K/ Akt signaling and promotes gastric cancer development 25 . Previous studies p‐PI3K can activate Akt to form p‐Akt, and then participate in the process of gastric cancer development and development 26‐30 . It was shown p‐PI3K and p‐Akt were reduced after Herceptin treatment in gastric cancer cells, and hsa_circ_0000520 overexpression could restrain p‐PI3K and p‐Akt level.…”

Section: Discussionmentioning

confidence: 91%

hsa_circ_0000520 influences herceptin resistance in gastric cancer cells through PI3K‐Akt signaling pathway

Wang

et al. 2020

Clinical Laboratory Analysis

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Background To investigate whether hsa_circ_0000520 affects Herceptin resistance in gastric cancer by regulating the PI3K‐AKT signaling. Methods The expression of hsa_circ_0000520 was detected by qRT‐PCR in gastric cancer tissues and cell lines. A Herceptin‐resistant gastric cancer cell was established. PcDNA and pcDNA‐hsa_circ_0000520 were transfected into NCI‐N87R cells and treated with Herceptin at a concentration of 10 μg/mL for 24 hours. MTT tested cell proliferation, and apoptosis was measured by flow cytometry. IGF‐1 treatment was used to activate PI3K‐Akt signaling. The expression levels of related proteins were detected. Results The expression of hsa_circ_0000520 was reduced in gastric cancer tissues and cell lines, and hsa_circ_0000520 in NCI‐N87R cells was significantly lower than that of NCI‐N87 cells. Compared with the CON group, the cell viability of the Herceptin group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of Bcl‐2, p‐PI3K, and p‐Akt protein were significantly reduced. Compared with the Herceptin + pcDNA group, the cell viability of the Herceptin + hsa_circ_0000520 group was significantly reduced, the apoptosis rate was significantly increased, the level of Bax protein was significantly increased, and the levels of p‐PI3K and p‐Akt proteins were significantly reduced. After IGF‐1 treatment, the cell viability was significantly increased, the apoptosis rate was significantly reduced, the level of Bax protein was significantly reduced, and the level of Bcl‐2 protein was significantly increased. Conclusion Hsa_circ_0000520 overexpression may reverse the Herceptin resistance of gastric cancer cells by inhibiting the PI3K‐Akt signaling pathway.

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Section: Discussionmentioning

confidence: 91%

hsa_circ_0000520 influences herceptin resistance in gastric cancer cells through PI3K‐Akt signaling pathway

Wang

et al. 2020

Clinical Laboratory Analysis

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“…The knockdown of NUDT1 could inhibit the migration of osteosarcoma cells [29]. And the knockdown of NUDT1 could also inhibit the migration of gastric cancer through PI3K/AKT pathway [30]. Therefore, overexpressed NUDT1 is quite associated with the migration of many kind of cancers.…”

Section: Discussionmentioning

confidence: 97%

NUDT1-Knockdown Inhibits Proliferation, Invasion and Migration of CAL27

Shan

2020

Preprint

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Background: The high level of reactive oxygen species (ROS) in cancer could oxidize guanine into 8-oxoG resulting in A: T changed into G: C or G: C into A: T. Nudix hydrolase 1 (NUDT1) overexpressed in many kind of cancers could hydrolyze the 8-oxo-dGTP into 8-oxo-dGMP or pyrophosphate to prevent the DNA damage or gene mutation. However, the role and function of NUDT1 in oral squamous cell carcinoma (OSCC) has not been investigated.Methods: Firstly, the bioinformatics methods were used to predict the biological process, cellular component and molecular function of NUDT1 and to confirm the mRNA and protein expression level of NUDT1 in OSCC. Furthermore, the MTT assay, Flow Cytometry, Transwell (Invasion), Scratch Test and Transwell (Migration) were used to test the effect of NUDT1 inhibitor on the proliferation, cell apoptosis, invasion and migration of CAL27. In addition, western blot was used to exam the expression level of NUDT1 and cleaved caspase-3 in different groups. Finally, the laser scanning microscope (LSM) was used to test the invadopodia formation level in different groups.Results: The bioinformatics analysis suggested that both mRNA and protein of NUDT1 overexpressed in head and neck squamous cell carcinoma (HNSCC) and OSCC. Furthermore, the biological process of NUDT1 mainly enriched in response to oxidative stress, aging, response to cadmium ion and male gonad development in OSCC. the cellular component of NUDT1 mainly enriched in extracellular exosome, cytoplasm, plasma membrane and nucleus in OSCC. The molecular function of NUDT1 mainly enriched in protein binding in OSCC. Finally, the biological experiments confirmed that NUDT1-knockdown could inhibit the proliferation, invasion, migration and promote cell apoptosis of CAL27.Conclusion: The overexpressed NUDT1 is positively associated with the progression of OSCC which has much potential to be new target in targeted therapy of OSCC.

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“…It also promotes the proliferation and malignant transformation of tumor cells through phosphorylation of PI3K and AKT protein and inhibits the apoptosis of tumor cells. More and more studies have reported that PI3K/AKT signaling pathway regulates the growth, apoptosis and invasion of tumor cells in malignant tumors of digestive system [27] .Previous studies p-PI3K can activate Akt to form p-Akt, and then participate in the process of gastric cancer development and development [28,29,30,31,32] .ZHANG et al [33] validated that YARS exerted its malignant roles in GC through activated PI3K-Akt signaling.KONG et al's [34] experiments showed that NOLC1 overexpression accelerated proliferation, migration, invasion, and cyclin B1 expression and inhibited the apoptosis and cleaved-caspase-3 expression of Esophageal carcinoma (ESCA) cells via activating PI3K/AKT pathway. CHENG et al [35] found blockage of Osteopontin (OPN) downregulates the activation of the PI3K-AKT-GSK/3b-b/catenin pathway, accompanied by the inhibition of CRC stem cell proportion.…”

Section: Discussionmentioning

confidence: 97%

The Construction and Analysis of ceRNA Network in H pylori infection atrophic gastritis

Bai¹,

Liang²,

Wang³

2021

Preprint

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Background：Chronic atrophic gastritis (CAG) is an established pre-cancerous lesion of intestinal type gastric cancer(GC),H pylori infection is the main pathogenic cause,this study intends to study the pathogenesis of atrophic gastritis(Hp+) from the lncRNA-miRNA-mRNA ceRNA regulatory network, in order to provide the oretical basis and data support for the treatment of atrophic gastritis.Results:GSE111762 downloaded from GEO database was used to analyze the differentially expressed lncRNAs and mRNAs(DEGs).A total of 395 differentially expressed lncRNA (225 upregulated,170 downregulated) and 1093 DEGs ( 674 upregulated, 419 downregulated) are obtained. Through the cross-mapping of miRcode, starBase, Sponescan,miRTarBase and miRBase databases,16 miRNAs were predicted,and the lncRNA-miRNA-mRNA ceRNA regulatory network consisting of 71 IncRNAs,16 miRNAs and 597 mRNAs was constructed.597 DEGs were analyzed by David database for functional enrichment. A total of 250 GO enrichment items were obtained, including 160 BP entries, 48 CC entries and 42 MF entries,29 signal pathways were obtained by enrichment analysis of KEGG pathways, mainly p53 signaling pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Using Cytoscape plug-in CytoHubba to filter 597 DEGs with "MCC, MNC, Degree" top20 as screening conditions, Eleven key hub targets are obtained from the intersection of jvenn.Protein interaction analysis of key hub targets through Cytoscape plug-in GeneMania, it was found that 87.65% displayed similar co-expression characteristics.Construct ceRNA regulatory network of the key hub targets,11 mRNAs(such as BRCA1, RAD54L),12 miRNAs(such as hsa-miR-340-5p,hsa-miR-182-5p) and 58 lncRNAs(such as PCGEM1,FTX) were predicted. Conclusions:Clarify the complex reticular regulation of atrophicgastritis with multi-targets, multi-pathways and multi-pathways.Which provides a new idea for the study of the mechanism of action of atrophicgastritis (Hp+) and a potential target for its treatment,thus to further early diagnosis and reversal of gastric cancer.

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MTH1 Inhibitor TH287 Suppresses Gastric Cancer Development Through the Regulation of PI3K/AKT Signaling

Cited by 9 publications

References 39 publications

hsa_circ_0000520 influences herceptin resistance in gastric cancer cells through PI3K‐Akt signaling pathway

hsa_circ_0000520 influences herceptin resistance in gastric cancer cells through PI3K‐Akt signaling pathway

NUDT1-Knockdown Inhibits Proliferation, Invasion and Migration of CAL27

The Construction and Analysis of ceRNA Network in H pylori infection atrophic gastritis

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