PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway

Ma, Zhan; Lou, Shuping; Jiang, Zheng

doi:10.18632/aging.103117

Cited by 105 publications

(65 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In gastric adenocarcinoma, the suppression of the PI3K/AKT/mTOR pathway activation is also considered to enhance apoptosis and autophagy in malignant cells 36 . In addition, the suppression of pleckstrin homology like domain family A member 2 in colorectal cancer contributes to enhanced cell apoptosis and autophagy by inactivating the PI3K/AKT/mTOR signaling pathway 37 . PKI‐402, an inhibitor of the PI3K/mTOR pathway, has also been proven to promote autophagy and result in an imbalance of Bcl‐2 family proteins in ovarian cancer 38 …”

Section: Discussionmentioning

confidence: 99%

The depletion of Circ‐PRKDC enhances autophagy and apoptosis in T‐cell acute lymphoblastic leukemia via microRNA‐653‐5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway

Zhang

Fang

et al. 2021

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

A range of circular (Circ) RNAs have been demonstrated to be of therapeutic significance for the treatment of acute lymphoblastic leukemia (ALL). Here, we investigated the mechanisms underlying the action of Circ-PRKDC and the microRNA-653-5p/ Reelin (miR-653-5p/RELN) axis in T-cell ALL (T-ALL).Clinical specimens were obtained from patients with T-ALL (n = 39) and healthy controls (n = 30). In each specimen, we determined the expression levels of Circ-PRKDC, miR-653-5p, and RELN. Human T-ALL cells (Jurkat) were transfected with Circ-PRKDC-or miR-653-5p-related sequences to investigate cell proliferation, apoptosis, and autophagy. We also determined the levels of Circ-PRKDC, miR-653-5p, RELN, and signaling proteins related to phosphoinositide 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). Finally, we decoded the interactions between Circ-PRKDC, miR-653-5p, and RELN. The expression levels of Circ-PRKDC and RELN were upregulated in T-ALL tissues and cells while the levels of miR-653-5p were downregulated. Thereafter, then silencing of Circ-PRKDC, or the enforced expression of miR-653-5p, repressed the expression of RELN and the activation of the PI3K/AKT/mTOR signaling pathway, thus enhancing cell autophagy and apoptosis, and disrupting cell proliferation. Circ-PRKDC acted a sponge for miR-653-5p while miR-653-5p targeted RELN. The knockdown of miR-653-5p abrogated the silencing of Circ-PRKDCinduced effects in T-ALL cells. The depletion of Circ-PRKDC elevated miR-653-5p to silence RELN-mediated PI3K/AKT/mTOR signaling activation, thereby enhancing autophagy and apoptosis in T-ALL cells.

show abstract

Section: Discussionmentioning

confidence: 99%

The depletion of Circ‐PRKDC enhances autophagy and apoptosis in T‐cell acute lymphoblastic leukemia via microRNA‐653‐5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway

Zhang

Fang

et al. 2021

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

show abstract

“…Ki67, Bax, Bcl-2, and caspase-3/9 are marker proteins related to proliferation and apoptosis. High Ki67 expression in tumor tissues is related to the promotion of tumor progression [26]. As a critical apoptotic executor downstream of the caspase cascade, the activation of caspase-3 largely depends on the release of Cyt-c. Bcl-2 and Bax, members of the Bcl-2 family, are the most important regulators of apoptosis [27].…”

Section: Discussionmentioning

confidence: 99%

WGCNA Co-Expression Network Analysis Reveals LncRNA LINC00313 Functions as A ceRNA to Regulate PTEN-Mediated PI3K/AKT Signaling Pathway by Sponging miR-19a-3p in Docetaxel-Resistant Prostate Cancer Cells

Chen

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Docetaxel is the preferred chemotherapeutic agent for patients with hormone-refractory PCa. LncRNAs play important roles in the development of docetaxel resistance in patients with PCa. We evaluated the effects of the lncRNA LINC00313 on growth and metastasis in docetaxel-resistant PCa cells, and the molecular mechanisms underlying these effects.Methods: The mRNA dataset (GSE102124 and GSE55945) and lncRNA dataset (GSE115414) were downloaded from the GEO database. The DEGs were identified using the “R package limma”. WGCNA were performed to identify the modules and genes associated with PCa. A PPI network was constructed using the STRING database and visualized using Cytoscape. The Cytohubba plug-in was used to identify the hub genes and cytoNCA plug-in was used to identify the highest linkage hub genes. Based on lncRNA-miRNA pairs and miRNA-mRNA pairs using StarBase and TargetScan databases, a ceRNA network was constructed. Functional analysis was performed via GO, GSEA, and GSVA analysis. Cell proliferation, apoptosis, cell cycle progression, migration, and invasion were evaluated by CCK-8, colony formation, flow cytometry, transwell, and wound healing assays. RT-PCR, western blot, and immunohistochemistry were used to evaluate mRNA and protein expression. The oncogenicity of LINC00313 in docetaxel-resistant PCa cells was determined by tumor transplantation in nude mice. Luciferase reporter and RNA pull-down assays were used to evaluate interactions between LINC00313 and miR-19a-3p as well as between miR-19a-3p and PTEN.Results: LINC00313-miR-19a-3p-PTEN was a core network of ceRNA network. Cox regression analysis identified LINC00313 as an independent prognostic variable for OS in patients with PCa. LINC00313 overexpression in docetaxel-resistant PCa cells suppressed proliferation, invasion, and migration, and induced apoptosis and cell cycle arrested at the G1 phase. These changes were related to changes in cyclinD1, p27, Ki67, Bax, Bcl-2, caspase-3/9, E-cadherin, N-cadherin, Vimentin, and MMP-2 expression. Animal experiments showed that LINC00313 silencing promoted tumor formation. Co-transfection with LINC00313‐WT and miR-19a-3p mimic reduced luciferase activity, and co-transfection with PTEN‐WT and LINC00313 increased luciferase activity. The effects of LINC00313, including increased PTEN, decreased PIP3 expression, and the inhibition of proliferation and metastasis in docetaxel-resistant PC cells, were abolished by miR-19a-3p mimic.Conclusion: LINC00313 overexpression suppressed the proliferation and metastasis of docetaxel-resistant PC cells by competitively binding to miR-19a-3p to regulate PTEN expression and inhibit the activation of the PI3K/Akt signaling pathway.

show abstract

“…PI3K/AKT signaling pathway regulates cell proliferation, apoptosis, migration, invasion and angiogenesis. AKT is the only protein downstream of PI3K that can promote malignant transformation of cells [30]. Activated AKT regulates the expression of caspase-3, Ki67, VEGF, and MMP-2/-9.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Yan¹,

Zhang²,

Yi³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Esophageal cancer (ESCC) is one of the most common malignant tumors in the digestive system. This study aims to explore the effects of sperm associated antigen 5 (SPAG5) on cell growth, metastasis, and azithromycin resistance in esophagus cancer and its molecular mechanism.Methods: The DEGs were obtained from GSE92396, GSE17351, and GSE9982 datasets about ESCC. The PPI network was constructed using the STRING database and was visualized using Cytoscape software. The cytohubba plug-in of Cytoscape software was used to identify the hub genes of the PPI network. The DEGs were used to perform GO and KEGG pathway enrichment analysis using the DAVID database. Statistical analysis was performed to test the clinical and prognostic significance of SPAG5. Cell viability, proliferation, apoptosis, migration, and invasion were detected using CCK-8, colony formation, flow cytometry, transwell and scratch-wound assays. The expression of related genes was detected by qRT-PCR, western blot and IHC assays. The oncogenicity of SPAG5 in ESCC cells was determined using the nude mouse transplantation tumor experiment.Results: Ninety-three overlapping genes from the DEGs were used to construct the PPI network, and mainly enriched in BP, CC, and MF terms. COX regression analysis of OS showed that SPAG5 expression and pN category were correlated with OS. Univariate and multivariate analyses showed that SPAG5 was an independent prognostic factor for OS in ESCC. The ROC curve analysis showed the AUC of SPAG5 was 0.74. Multiple logistic regression showed that SPAG5 were subsequently identified as an independent risk factor associated with OS. SPAG5 overexpression was detected in ESCC tissues and cell lines, and improved cell proliferation. SPAG5 knockdown reduced cell growth and metastasis and promoted its apoptosis. The functions of SPAG5 overexpression promoting ESCC cell growth and affecting cleaved caspase-3, Ki67, VEGF, and MMP-2/-9 expression were reversed by PI3K/AKT inhibitor. SPAG5 overexpression enhanced resistance to ADM in EC9706 and Eca109 cells and it was closely related to the activation of PI3K/AKT signaling pathway.Conclusion: The overexpression of SPAG5 was an independent good prognostic factor and promoted the proliferation, invasion, migration, and ADM resistance, and inhibited the apoptosis via activating PI3K/AKT signaling pathway in ESCC.

show abstract

PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway

Cited by 105 publications

References 44 publications

The depletion of Circ‐PRKDC enhances autophagy and apoptosis in T‐cell acute lymphoblastic leukemia via microRNA‐653‐5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway

The depletion of Circ‐PRKDC enhances autophagy and apoptosis in T‐cell acute lymphoblastic leukemia via microRNA‐653‐5p/Reelin mediation of the PI3K/AKT/mTOR signaling pathway

WGCNA Co-Expression Network Analysis Reveals LncRNA LINC00313 Functions as A ceRNA to Regulate PTEN-Mediated PI3K/AKT Signaling Pathway by Sponging miR-19a-3p in Docetaxel-Resistant Prostate Cancer Cells

Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

Contact Info

Product

Resources

About