SIRT1 suppresses the migration and invasion of gastric cancer by regulating ARHGAP5 expression

Dong, Guoying; Wang, Bo; An, Yifei; Li, Juan; Wang, Xin; Jia, Jihui; Yang, Qing

doi:10.1038/s41419-018-1033-8

Cited by 48 publications

(41 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies has reported that SLC14A1 was regard as a novel target for human urothelial cancer [48] and urinary bladder cancer [49]. However, Rho GTPase activating protein 5 (ARHGAP5) was identified as an oncogene that affected cell migration and invasion in cervical cancer [50], gastric cancer [51] and nasopharyngeal carcinoma [52]. Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutation has found in hematological malignancies [53], including acute myeloid leukemia [54] and diffuse large B cell lymphoma [55].…”

Section: Discussionmentioning

confidence: 99%

Identification of the key genes and microRNAs in adult acute myeloid leukemia with FLT3 mutation by bioinformatics analysis

Chen¹,

Chen²,

Zhu³

et al. 2020

Int. J. Med. Sci.

View full text Add to dashboard Cite

Background: Associated with poor prognosis, FMS-like tyrosine kinase 3 (FLT3) mutation appeared frequently in acute myeloid leukemia (AML). Herein, we aimed to identify the key genes and miRNAs involved in adult AML with FLT3 mutation and find possible therapeutic targets for improving treatment. Materials: Gene and miRNA expression data and survival profiles were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. EdgeR of R platform was applied to identify the differentially expressed genes and miRNAs (DEGs, DE-miRNAs). Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape and DAVID. And protein-protein interaction network, miRNA-mRNA regulatory network and clustering modules analyses were performed by STRING database and Cytoscape software. Results: Survival analysis showed FLT3 mutation led to adverse outcome in AML. 24 DE-miRNAs (6 upregulated, 18 downregulated) and 250 DEGs (54 upregulated, 196 downregulated) were identified. Five miRNAs had prognostic value and the results matched their expression levels (miR-1-3p, miR-10a-3p, miR-10a-5p, miR-133a-3p and miR-99b-5p). GO analysis showed DEGs were enriched in skeletal system development, blood vessel development, cartilage development, tissue morphogenesis, cartilage morphogenesis, cell morphogenesis involved in differentiation, response to growth factor, cell-substrate adhesion and so on. The KEGG analysis showed DEGs were enriched in PI3K-Akt signaling pathway, ECM-receptor interaction and focal adhesion. Seven genes (LAMC1, COL3A1, APOB, COL1A2, APP, SPP1 and FSTL1) were simultaneously identified by hub gene analysis and module analysis. SLC14A1, ARHGAP5 and PIK3CA, the target genes of miR-10a-3p, resulted in poor prognosis. Conclusion: Our study successfully identified molecular markers, processes and pathways affected by FLT3 mutation in AML. Furthermore, miR-10a-3p, a novel oncogene, might involve in the development of FLT3 mutation adult AML by targeting SLC14A1, ARHGAP5 and PIK3CA.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of the key genes and microRNAs in adult acute myeloid leukemia with FLT3 mutation by bioinformatics analysis

Chen¹,

Chen²,

Zhu³

et al. 2020

Int. J. Med. Sci.

View full text Add to dashboard Cite

show abstract

“…Studies showed that silencing SIRT1 inhibited cell proliferation and tumor formation in some human cancer cell lines such as non‐small‐cell lung cancer and breast cancer (Abdolvahabi et al., ; Xu et al., ). But another studies claimed that SIRT1 inhibits tumor progression and invasion in human gastric cancer cell lines (Dong et al., ). Thus, it remains controversial whether SIRT1 acts as a tumor promoter or suppressor.…”

Section: Discussionmentioning

confidence: 99%

Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666‐1 cells through regulating PARP‐2/SIRT1/AMPK signaling pathway

Zheng

Chao

et al. 2019

Food Science & Nutrition

View full text Add to dashboard Cite

Background/Aim Nobiletin, a major polymethoxyflavones ( PMF s) from citri reticulatae pericarpium ( CRP ), can inhibit several forms of cancer proliferation. However, the effects of nobiletin on nasopharyngeal carcinoma ( NPC ) C666‐1 cells remain largely unknown. Materials and Methods Cell counting kit 8 ( CCK 8) assay was used to measure cell vitality. Flow cytometry was performed to measure the apoptosis rate. Quantitative real‐time polymerase chain reaction ( qRT ‐ PCR ) and Western blot analysis were applied to determine the expression of mRNA and protein, respectively. Results We showed that the proliferation rate of C666‐1 cells was inhibited and the apoptosis rate was raised after treating with nobiletin. Moreover, nobiletin inhibited the expression of poly( ADP ‐ribose)polymerase‐2 ( PARP ‐2), and the tumor suppression effect of nobiletin on C666‐1 is associated with PARP ‐2‐dependent pathway. Conclusion We demonstrated for the first time that nobiletin inhibited the growth of C666‐1 cells, which may be relative to its regulation on PARP ‐2/ SIRT 1/ AMPK signaling pathway. Our result implied that nobiletin may serve as a strategy to treat nasopharyngeal carcinoma.

show abstract

“…FHRE-Luc (#1789, Addgene) was a luciferase construct containing three copies of forkhead response elements 43 . The relative luciferase activities were measured and calculated as previously described 44 .…”

Section: Luciferase Assaymentioning

confidence: 99%

“…ChIP assays were performed as previously described 44 with anti-FOXO3a-ChIP Grade (ab12162, Abcam). Coprecipitated DNA served as the template for amplification of the AMPKα and AMPKγ promoters.…”

Section: Chromatin Immunoprecipitation (Chip)mentioning

confidence: 99%

SIRT1 inhibits chemoresistance and cancer stemness of gastric cancer by initiating an AMPK/FOXO3 positive feedback loop

Wang

et al. 2020

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Chemotherapy is the standard care for patients with gastric cancer (GC); however, resistance to existing drugs has limited its success. The persistence of cancer stem cells (CSCs) is considered to be responsible for treatment failure. In this study, we demonstrated that SIRT1 expression was significantly downregulated in GC tissues, and that a low SIRT1 expression level indicated a poor prognosis in GC patients. We observed a suppressive role of SIRT1 in chemoresistance of GC both in vitro and in vivo. In addition, we found that SIRT1 eliminated CSC properties of GC cells. Mechanistically, SIRT1 exerted inhibitory activities on chemoresistance and CSC properties through FOXO3 and AMPK. Furthermore, a synergistic effect was revealed between FOXO3 and AMPK. AMPK promoted nuclear translocation of FOXO3 and enhanced its transcriptional activities. In addition, FOXO3 increased the expression level and activation of AMPKα by directly binding to its promoter and activating the transcription of AMPKα. Similar to SIRT1, low expression levels of p-AMPKα and FOXO3a are also related to the poor prognosis of GC patients. Moreover, we revealed a correlation between the expression levels of SIRT1, p-AMPKα, and FOXO3a. These findings indicated the importance of the SIRT1-AMPK/FOXO3 pathway in reversing chemoresistance and CSC properties of GC. Thus, exploring efficient strategies to activate the SIRT1-AMPK/FOXO3 pathway may lead to improving the survival of GC patients.

show abstract

SIRT1 suppresses the migration and invasion of gastric cancer by regulating ARHGAP5 expression

Cited by 48 publications

References 36 publications

Identification of the key genes and microRNAs in adult acute myeloid leukemia with FLT3 mutation by bioinformatics analysis

Identification of the key genes and microRNAs in adult acute myeloid leukemia with FLT3 mutation by bioinformatics analysis

Nobiletin induces growth inhibition and apoptosis in human nasopharyngeal carcinoma C666‐1 cells through regulating PARP‐2/SIRT1/AMPK signaling pathway

SIRT1 inhibits chemoresistance and cancer stemness of gastric cancer by initiating an AMPK/FOXO3 positive feedback loop

Contact Info

Product

Resources

About