Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P31749 (AKT)
 22,954 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, sperm-associated antigen 6 (SPAG6), a member of the cancer-testis antigen family, has been shown to be involved in tumorigenesis. An increasing number of studies have shown that SPAG6 expression is associated with the pathogenesis of myelodysplastic syndrome (MDS). However, the mechanism has not been clearly elucidated. Our previous results indicated that SPAG6 affected cell apoptosis in MDS. In this study, we used reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to demonstrate that the mRNA expression of SPAG6 in bone marrow cells of patients with MDS or MDS-derived acute myeloid leukemia (MDS-AML) was higher than that of cancer-free patients. Kaplan-Meier survival curve analysis of published AML found that patients with high expression of SPAG6 had poor survival. The results of the cell counting kit-8, FACS, RT-qPCR, and Western blotting assays indicated that SPAG6 knockdown in the SKM-1 cell line inhibited cell proliferation, and affected cell cycle and differentiation. Furthermore, we found that SPAG6 knockdown affected the proliferation of SKM-1 cells by mediating the G1-to-S transition of the cell cycle. Moreover, we demonstrated that the antiproliferative effect of SPAG6 knockdown was associated with the upregulation of the cyclin-dependent kinase inhibitor p27Kip1, and regulation of the AKT/FOXO pathway. These findings indicated that SPAG6 might be a potential therapeutic target.
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PMID:Upregulation of SPAG6 in Myelodysplastic Syndrome: Knockdown Inhibits Cell Proliferation via AKT/FOXO Signaling Pathway. 3083 46

Objective: PI3K/AKT signal pathway is important for negative regulation of FoxO3a/p27Kip1, maintaining cell survival and inhibiting apoptosis. Phosphatase and tensin homology deleted on chromosome 10 (PTEN) gene negatively regulates PI3K/AKT signal pathway. It's downregulation is correlated with prostate cancer (PC) pathogenesis. Previous study showed significantly elevated miR-26a expression in PC tissues, indicating its tumor facilitating role in PC. Bioinformatics analysis revealed targeted relationship between miR-26a and 3'-UTR of PTEN mRNA. This study investigated if miR-26a and PTEN dysregulation played a role in proliferation and apoptosis of PC-3 cells. Materials and Methods: PC tumor tissues were collected along with benign prostate hyperplasia samples. Expression of miR-26a and PTEN was detected. The targeted relationship between miR-26a and PTEN was analyzed by dual-luciferase reporter gene assay. In vitro-cultured PC-3 cells were treated with miR-26a inhibitor and/or pIRES2-PTEN. Flow cytometry was employed to detect cell apoptosis, cycle, and Ki-67 expression. Expression of miR-26a and PTEN was analyzed. Western blot was employed to detect protein levels of p-AKT, p-FoxO3a, and p27Kip1. Results: PC tissues had elevated miR-26a expression and lower PTEN expression compared with benign hyperplasia. miR-26a targeted and inhibited PTEN expression. Transfection of miR-26a inhibitor and/or overexpression of PTEN significantly decreased phosphorylation activity of AKT and FoxO3a, enhanced p27Kip1 expression, cell apoptosis, weakened proliferation ability, and arrested cell cycle at G0/G1 phase. Conclusions: PC tissue had higher miR-26a and lower PTEN expressions. miR-26a targeted and inhibited PTEN, potentiated phosphorylation activity of AKT and FoxO3a, downregulated p27Kip1 expression, decreased cell apoptosis, and facilitated proliferation.
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PMID:Targeted Regulation of miR-26a on PTEN to Affect Proliferation and Apoptosis of Prostate Cancer Cells. 3113 80


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