TP53/miR-34a-associated signaling targets SERPINE1 expression in human pancreatic cancer

Akula, Shaw M.; Ruvolo, Peter P.; McCubrey, James A.

doi:10.18632/aging.102776

Cited by 21 publications

(14 citation statements)

References 80 publications

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“…It is regulated by TP53 in many cells. We have previously shown that serpine-1 is regulated by TP53/miR-34a in MIA-PaCa-2 cells as well as primary PDAC patient samples [68]. Tiplaxtinin is a serpine-1 inhibitor [69].…”

Section: Effects Of Wt-gsk-3β and Kd-gsk-3β On The Sensitivities To Dmentioning

confidence: 99%

GSK-3β Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutraceuticals

Abrams

Akula

Meher

et al. 2021

Cells

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Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3β in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3β. Transfection of MIA-PaCa-2 cells with WT-GSK-3β increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3β often increased therapeutic sensitivity. An exception was observed with cells transfected with WT-GSK-3β and sensitivity to the BCL2/BCLXL ABT737 inhibitor. WT-GSK-3β reduced glycolytic capacity of the cells but did not affect the basal glycolysis and mitochondrial respiration. KD-GSK-3β decreased both basal glycolysis and glycolytic capacity and reduced mitochondrial respiration in MIA-PaCa-2 cells. As a comparison, the effects of GSK-3 on MCF-7 breast cancer cells, which have mutant PIK3CA, were examined. KD-GSK-3β increased the resistance of MCF-7 cells to chemotherapeutic drugs and certain signal transduction inhibitors. Thus, altering the levels of GSK-3β can have dramatic effects on sensitivity to drugs and signal transduction inhibitors which may be influenced by the background of the tumor.

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Section: Effects Of Wt-gsk-3β and Kd-gsk-3β On The Sensitivities To Dmentioning

confidence: 99%

GSK-3β Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutraceuticals

Abrams

Akula

Meher

et al. 2021

Cells

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View full text Add to dashboard Cite

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“…Except for CRC, some of these genes have also been found to be associated with the progression of other cancers. For instance, SERPINE1, a critical target of the TP53/miR‐34a axis affecting the malignant characteristics of pancreatic ductal adenocarcinoma (PDAC), may become a potential biomarker for early detection 27 . Upon liver injury, NOX1 gene of liver macrophages was activated by damage‐associated molecular patterns secreted by dying hepatocytes to accelerate the development of hepatoma 28 .…”

Section: Discussionmentioning

confidence: 99%

A novel epithelial‐mesenchymal transition molecular signature predicts the oncological outcomes in colorectal cancer

Shan

Yan

et al. 2021

J Cellular Molecular Medi

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Epithelial‐mesenchymal transition (EMT), a biological process involving the transformation of epithelial cells into mesenchymal cells, promotes tumour initiation and metastasis. The aim of this study was to construct an EMT molecular signature for predicting colorectal cancer (CRC) prognosis and evaluate the efficacy of the model. The risk scoring system, constructed by log‐rank test and multivariate Cox regression analysis according to EMT‐related gene expression in CRC patients from TCGA database, demonstrated the highest correlation with prognosis compared with other parameters in CRC patients. The risk scores were significantly correlated with more lymph node metastasis, distal metastasis and advanced clinical stage of CRC. The model was further successfully validated in two independent external cohorts from GEO database. Furthermore, we developed a nomogram to integrate the EMT signature with the pathological stage of CRC, which was found to perform well in predicting the overall survival. Additionally, this risk scoring model was found to be associated with immune cell infiltration, implying a potential role of EMT involved in immunity regulation in tumour microenvironment. Taken together, our novel EMT molecular model may be useful in identifying high‐risk patients who need an intensive follow‐up and more aggressive therapy, finally contributing to more precise individualized therapeutic strategies.

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“…MiR-34a, as a post-transcriptional regulator, is expressed in a variety of leukemia cells and other tumour cells [34,35]. Additionally, miR-34a may be used as a predictive marker for the future development of Richter syndrome in patients with chronic lymphocytic leukemia [36].…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles derived from T-cell acute lymphoblastic leukemia inhibit osteogenic differentiation of bone marrow mesenchymal stem cells <i>via</i> miR-34a-5p

et al. 2021

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Reduced bone formation in patients with T-cell acute lymphoblastic leukemia (T-ALL) may be related to the interaction between tumour cells and bone marrow stromal cells (BMSCs). The miRNAs in extracellular vesicles derived from leukemia cells play an essential role in regulating the function of BMSCs; however, the regulatory mechanisms remain unclear. The expression of miR-34a-5p in T-ALL patients and cells was measured by quantitative real-time PCR. BMSCs were co-cultured with extracellular vesicles isolated from T-ALL cells in mineralization medium. The osteogenic differentiation of BMSCs was evaluated by Alizarin Red S staining, alkaline phosphatase (ALP) staining, and detection of osteogenic differentiation markers. A dual-luciferase reporter assay was performed to confirm the targeting relationship between miR-34a-5p and Wnt family member 1 (WNT1). MiR-34a-5p expression was upregulated in T-ALL patients and Jurkat cells. After BMSCs were co-cultured with extracellular vesicles derived from T-ALL cells, osteogenic differentiation of BMSCs was inhibited, and bone mineralization and ALP activity were decreased compared to those of control cells. MiR-34a-5p knockdown in T-ALL cells restored osteogenic differentiation of BMSCs co-cultured with extracellular vesicles. In addition, miR-34a-5p targets and negatively regulates WNT1 expression. In conclusion, our results demonstrated that knockdown of miR-34a-5p in extracellular vesicles derived from T-ALL cells promoted osteogenic differentiation of BMSCs by regulating WNT1.

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TP53/miR-34a-associated signaling targets SERPINE1 expression in human pancreatic cancer

Cited by 21 publications

References 80 publications

GSK-3β Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutraceuticals

GSK-3β Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutraceuticals

A novel epithelial‐mesenchymal transition molecular signature predicts the oncological outcomes in colorectal cancer

Extracellular vesicles derived from T-cell acute lymphoblastic leukemia inhibit osteogenic differentiation of bone marrow mesenchymal stem cells <i>via</i> miR-34a-5p

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