NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K/Akt/mTOR signaling pathway

Huang, Yakai; Kang, Weiming; Ma, Zhiqiang; Liu, Yuqin; Zhou, Li; Yu, Jian-chun

doi:10.1093/carcin/bgy142

Cited by 47 publications

(45 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 a). This results are consistent with the reported role of NUCKS in the induction of apoptosis in gastric cancer cells [ 29 ]. The light microscope images showed that cells changed morphology and displayed high number of vacuoles after silencing NUCKS (Fig.…”

Section: Resultssupporting

confidence: 93%

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

Zhao

Feng

Bai

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background Nuclear casein kinase and cyclin-dependent kinase substrate (NUCKS), a novel gene first reported in 2001, is a member of the high mobility group (HMG) family. Although very little is known regarding the biological roles of NUCKS, emerging clinical evidence suggests that the NUCKS protein can be used as a biomarker and therapeutic target in various human ailments, including several types of cancer. Methods We first assessed the potential correlation between NUCKS expression and gastric cancer prognosis. Then functional experiments were conducted to evaluate the effects of NUCKS in cell proliferation, cell cycle, apoptosis and autophagy. Finally, the roles of NUCKS on gastric cancer were examined in vivo. Results We found that NUCKS was overexpressed in gastric cancer patients with poor prognosis. Through manipulating NUCKS expression, it was observed to be positively associated with cell proliferation in vitro and in vivo. NUCKS knockdown could induce cell cycle arrest and apoptosis. Then further investigation indicated that NUCKS knockdown could also significantly induce a marked increase in autophagy though the mTOR-Beclin1 pathway, which could be was rescued by NUCKS restoration. Moreover, silencing Beclin1 in NUCKS knockdown cells or adding rapamycin in NUCKS-overexpressed cells also confirmed these results. Conclusions Our findings revealed that NUCKS functions as an oncogene and an inhibitor of autophagy in gastric cancer. Thus, the downregulation or inhibition of NUCKS may be a potential therapeutic strategy for gastric cancer.

show abstract

Section: Resultssupporting

confidence: 93%

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

Zhao

Feng

Bai

et al. 2020

J Exp Clin Cancer Res

View full text Add to dashboard Cite

show abstract

“…The top 15 GO biological process terms and top 10 KEGG pathways of upregulated and downregulated genes, basing on the p ‐values, were chosen for biological function analysis (Figure ). Among these pathways, the JAK‐STAT, MAPK, and PI3K‐Akt signaling pathways and ECM‐receptor interactions have been reported to be correlated with the proliferation, invasion, and metastasis of cancer in patients …”

Section: Resultsmentioning

confidence: 99%

“…The enriched KEGG pathways with upregulated expression of DEmRNAs included the p53 signaling pathway, ECM‐receptor interaction, and PI3K‐Akt signaling pathway. The pathways with downregulated expression of DEmRNAs included the JAK‐STAT signaling pathway and MAPK signaling pathway, which were previously found to be associated with malignant tumors . The PI3K‐Akt signaling pathway has been shown to participate in cell proliferation, migration, differentiation, survival, and trafficking in vitro …”

Section: Discussionmentioning

confidence: 95%

“…The pathways with downregulated expression of DEmRNAs included the JAK-STAT signaling pathway and MAPK signaling pathway, which were previously found to be associated with malignant tumors. [34][35][36][37]43 The PI3K-Akt signaling pathway has been shown to participate in cell proliferation, migration, differentiation, survival, and trafficking in vitro. 44 Through our module analysis of the PPI network, the mRNAs in the main modules were used as the core genes to further extract a subnetwork from the entire ceRNA network.…”

Section: Discussionmentioning

confidence: 99%

“…Among these pathways, the JAK-STAT, MAPK, and PI3K-Akt signaling pathways and ECM-receptor interactions have been reported to be correlated with the proliferation, invasion, and metastasis of cancer in patients. [34][35][36][37]…”

Section: Functional Analysis Of the Cerna Network-associated Demrnasmentioning

confidence: 99%

See 2 more Smart Citations

Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer

et al. 2020

Cancer Medicine

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA‐related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA‐miRNA‐mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer‐specific differentially expressed lncRNAs, miRNAs, and mRNAs were screened for constructing a ceRNA network using bioinformatic tools. The enrichment analysis of the biological processes in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathways was performed on the ceRNA‐related DEmRNAs. According to the modularization of protein‐protein interaction (PPI) network, we extracted a ceRNA subnetwork and analyzed the correlation between the expression of the lncRNAs involved and specific clinical features of patients. Next, the expression of highly up‐regulated in liver cancer (HULC) and RP11‐314B1.2 showed significant changes in several pathological processes involved in gastric cancer, and nine lncRNAs were found to be correlated with the overall survival of patients with gastric cancer. Through the univariate and multivariate Cox regression analyses, two lncRNAs (LINC00106 and RP11‐999E24.3) were identified and utilized to establish a risk score model for assessing the prognosis of patients. The analysis results were also partially verified using quantitative real‐time PCR. The findings from this study indicate that HULC, RP11‐314B1.2, LINC00106, and RP11‐999E24.3 could be considered as potential therapeutic targets or prognostic biomarkers in gastric cancer, and provide a new perspective for cancer pathogenesis research.

show abstract

Detailed role of microRNA‐mediated regulation of PI3K/AKT axis in human tumors

Al‐Hawary,

Ruzibakieva,

Gupta

et al. 2023

Cell Biochemistry & Function

View full text Add to dashboard Cite

The regulation of signal transmission and biological processes, such as cell proliferation, apoptosis, metabolism, migration, and angiogenesis are greatly influenced by the PI3K/AKT signaling pathway. Highly conserved endogenous non‐protein‐coding RNAs known as microRNAs (miRNAs) have the ability to regulate gene expression by inhibiting mRNA translation or mRNA degradation. MiRNAs serve key role in PI3K/AKT pathway as upstream or downstream target, and aberrant activation of this pathway contributes to the development of cancers. A growing body of research shows that miRNAs can control the PI3K/AKT pathway to control the biological processes within cells. The expression of genes linked to cancers can be controlled by the miRNA/PI3K/AKT axis, which in turn controls the development of cancer. There is also a strong correlation between the expression of miRNAs linked to the PI3K/AKT pathway and numerous clinical traits. Moreover, PI3K/AKT pathway‐associated miRNAs are potential biomarkers for cancer diagnosis, therapy, and prognostic evaluation. The role and clinical applications of the PI3K/AKT pathway and miRNA/PI3K/AKT axis in the emergence of cancers are reviewed in this article.

show abstract

NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K/Akt/mTOR signaling pathway

Cited by 47 publications

References 46 publications

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer

Detailed role of microRNA‐mediated regulation of PI3K/AKT axis in human tumors

Contact Info

Product

Resources

About