High developmental pluripotency‑associated 4 expression promotes cell proliferation and glycolysis, and predicts poor prognosis in non‑small‑cell lung cancer.

08:00 EDT 22nd May 2019 | BioPortfolio

Summary of "High developmental pluripotency‑associated 4 expression promotes cell proliferation and glycolysis, and predicts poor prognosis in non‑small‑cell lung cancer."

The developmental pluripotency‑associated 4 (Dppa4) gene serves critical roles in cell self‑renewal, as well as in cancer development and progression. However, the regulatory role of Dppa4 in non‑small‑cell lung cancer (NSCLC) and its underlying mechanisms remain elusive. The aim of the present study was to investigate the biological function of Dppa4 in NSCLC and its underlying mechanism of action. Dppa4 expression was measured in NSCLC tissue samples and cell lines, and its effect on cell proliferation and the expression of glycolytic enzymes was determined. In addition, the underlying mechanisms of Dppa4‑induced alterations in glycolysis were analyzed. Univariate and multivariate analyses were also performed to analyze the prognostic significance of clinicopathological characteristics. Dppa4 was found to be highly expressed in NSCLC tissues and cell lines. Furthermore, it was observed that Dppa4 was correlated with the degree of tumor differentiation and TNM stage. Univariate and multivariate analyses identified Dppa4 expression and clinical stage as prognostic factors for NSCLC patients. Kaplan‑Meier analysis further revealed that patients with lower Dppa4 expression exhibited a better prognosis. In NSCLC cells, Dppa4 knockdown inhibited cell proliferation, while Dppa4 overexpression enhanced cell proliferation, which was likely mediated by glycolysis promotion. Dppa4 knockdown had no evident effect on the majority of enzymes examined; however, glucose transporter type 4 (GLUT‑4) and pyruvate kinase isozyme M2 were significantly upregulated, and hexokinase II (HK‑II) and lactate dehydrogenase B (LDHB) were downregulated following Dppa4 knockdown. By contrast, Dppa4 overexpression resulted in downregulation of GLUT‑4, and upregulation of HK‑II, enolase and LDHB, whereas it had no effect on other enzymes. Since the most evident effect was observed on LDHB, further functional experiments demonstrated that this enzyme reversed the promoting effects of Dppa4 in NSCLC. In conclusion, Dppa4 promotes NSCLC progression, partly through glycolysis by LDHB. Thus, the Dppa4‑LDHB axis critically contributes to glycolysis in NSCLC cells, thereby promoting NSCLC development and progression.


Journal Details

This article was published in the following journal.

Name: Molecular medicine reports
ISSN: 1791-3004


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Medical and Biotech [MESH] Definitions

A homeodomain protein and transcription regulator that functions in BLASTOCYST INNER CELL MASS and EMBRYONIC STEM CELL proliferation and CELL SELF RENEWAL. It confers pluripotency on embryonic stem cells and prevents their differentiation towards extraembryonic ENDODERM and trophectoderm (TROPHOBLAST) CELL LINEAGES.

A proteolytically-cleaved membrane glycoprotein and member of the TNF superfamily that is highly expressed in a variety of tissues including heart, pancreas, brain, and peripheral blood lymphocytes. The secreted extracellular form is a weak inducer of APOPTOSIS for some cell types and a ligand for the FN14 RECEPTOR. It mediates activation of NF-KAPPA-B and promotes ANGIOGENESIS and proliferation of ENDOTHELIAL CELLS, as well as expression of cytokines involved in INFLAMMATION.

A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.

A family of calcium-independent cell adhesion molecules of the immunoglobulin superfamily. They are expressed by most cell types and mediate both homotypic and heterotypic cell-cell adhesion. Nectins function in a variety of morphogenetic and developmental processes that include organogenesis of the eye, ear, tooth, and cerebral cortex; they also play roles in viral infection and cell proliferation.

A transcription factor characterized by N-terminal and C-terminal CYS2-HIS2 ZINC FINGERS separated by a homeobox. It represses the expression of E-CADHERIN to induce the EPITHELIAL-MESENCHYMAL TRANSITION. It also represses PROTO-ONCOGENE PROTEINS C-BCL-6; regulates the cell type-specific expression of SODIUM-POTASSIUM-EXCHANGING ATPASE; and promotes neuronal differentiation.

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