The present study aimed to investigate the underlying functions of CagA in human gastric cancer, and to explore the associations between CagA, PTEN and Tet1 in gastric cancer.
Western blotting and the Luciferase Reporter Assay were used to evaluate the change of PTEN expression after lowered expression of miR-21 in gastric cancer cell lines.
As PTEN is a potential modifier of tumour response to trastuzumab, a recently approved therapy in metastatic HER2 positive gastric cancer, the existence of PTEN deletions in primary gastric cancer was investigated.
The mechanism analyses further found that SLC25A5-AS1 might act as a competing endogenous RNAs (ceRNA), which was involved in the derepression of PTEN expression, a target gene of miR-19a-3p, and regulate malignant phenotype via PI3K/AKT signalling pathway in GC.
Taken together, these results suggest that PTENP1 functions as a novel tumor suppressor in GC and its suppressive ability may be involved in the modulation of PTEN.
Our data revealed that AKT1 mRNA and protein expression were induced by doxorubicin (a chemotherapeutic agent); the doxorubicin-induced AKT1 expression and activation increased the binding of NF-kappaB on Notch1 DNA promoter and then promoted the Notch1 transcription and expression; enhanced expression of Notch1 further upregulated PTEN expression through CBF-1 binding to PTEN DNA promoter; and inhibition of AKT1 expression and activity sensitized the gastric cancer cell to doxorubicin treatment in cultured gastric cancer cell lines and xenograft nude mice gastric cancer model.
Taken together, our results demonstrated that WWP2 promotes proliferation of GC cells by downregulating PTEN, which may provide new therapeutic targets for GC.
Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to examine miR-21 and phosphatase and tensin homolog (PTEN) and Sprouty2 expression in GC cell lines.
Our results indicated that PI3KCA mutation is an important determinant of response to AKT inhibition in GC and combination with AZD5363 can overcome innate resistance to Taxotere in a PTEN loss PDGCX model.
Therefore, our study revealed the mechanistic links between miR‑370 and PTEN in the pathogenesis of gastric cancer through modulation of cell apoptosis and proliferation.
Taken together, our results demonstrate that miR-188-5p promotes GC cell proliferation and migration while suppressing tumor suppressor gene PTEN expression via transcriptional upregulation of oncogene SALL4.
This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, and emphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.
The HOTAIR/miR-17-5p/PTEN axis could be regarded as the potential treatment targets for gastric cancer, and adjuvant therapy of SQFZ injection could assist in further improving the treatment efficacy of chemo-therapies for gastric cancer.
Frequent activation of phosphatidylinositol-3 kinases (PI3K)/Akt/mTOR signaling pathway in gastric cancer (GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3CA gene or loss of function of PTEN, a tumor suppressor protein, to name a few; both playing a crucial role in regulating this pathway.
The decreased expression of PTEN and E-cadherin, together with the overexpression of PI3K, AKT, MMP-2, MMP-9 and NF-kappaBp65, contributed cooperatively to the accelerated progress of gastric cancer.