LDHA Promotes Oral Squamous Cell Carcinoma Progression Through Facilitating Glycolysis and Epithelial–Mesenchymal Transition

Cai, Hao; Li, Jiaxin; Zhang, Yadong; Liao, Yan; Zhu, Yue; Wang, Cheng; Hou, Jinsong

doi:10.3389/fonc.2019.01446

Cited by 79 publications

(75 citation statements)

References 45 publications

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“…Additionally, GLUT1 has been found to be overexpressed in kidney cancer (Chan et al, 2011 ), liver cancer (Amann et al, 2009 ), ovarian cancer (Semaan et al, 2011 ), and other cancers. In oral squamous cell carcinoma (OSCC), lactate dehydrogenase A ( LDHA ) can facilitate glycolysis and epithelial-mesenchymal transition, thereby promoting the invasion and proliferation of OSCC cells (Cai et al, 2019 ). As a key rate-limiting enzyme in glycolysis, Pyruvate kinase M2 ( PKM2 ) can catalyze the conversion of phosphoenolpyruvate to pyruvate.…”

Section: Introductionmentioning

confidence: 99%

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

et al. 2021

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Background: Glycolysis is critical in the occurrence and development of tumors. Owing to the biological and clinical heterogeneity of patients with BRCA, the traditional predictive classification system is far from satisfactory. Survival and prognosis biomarkers related to glycolysis have broad application prospects for assessing the risk of patients and guiding their individualized treatment.Methods: The mRNA expression profiles and clinical information of patients with BRCA were obtained from TCGA database, and glycolysis-related genes were obtained by GSEA. Patients with BRCA were randomly divided into the training cohort and testing cohort. Univariate and multivariate Cox analyses were used to establish and validate a new mRNA signature for predicting the prognosis of patients with BRCA.Results: We established a four-gene breast cancer prediction signature that included PGK1, SDHC, PFKL, and NUP43. The patients with BRCA in the training cohort and testing cohort were divided into high-risk and low-risk groups based on the signature. The AUC values were 0.74 (training cohort), 0.806 (testing cohort) and 0.769 (entire cohort), thereby showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that four-gene signature could independently predict the prognosis of BRCA patients without being affected by clinical factors.Conclusion: We constructed a four-gene signature to predict the prognosis of patients with BRCA. This signature will aid in the early diagnosis and personalized treatment of breast cancer, but the specific associated biological mechanism requires further study.

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Section: Introductionmentioning

confidence: 99%

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

et al. 2021

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“…Many papers have described lactate produced by lactate dehydrogenase as triggering EMT in several cancer cells [18][19][20]. Several studies have also examined the relationships between lactate, EMT, and fibrosis [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Effect of lactate as a peritoneal dialysis fluid buffer on rat peritoneal mesothelial cells

2020

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Background Neutral, low-glucose degradation product (GDP) peritoneal dialysis fluid (PDF) is less damaging to the peritoneum than conventional PDF but is still insufficient for biocompatibility. One remaining issue is the problem of buffering. Methods Using cultured rat peritoneal mesothelial cells (PMCs), the present study examined the difference between the effects of neutral low-GDP lactate PDF and neutral low-GDP bicarbonate/lactate PDF on cells. The effects of lactate stimulation on these cells were also examined. Results Lactate PDF enhanced mRNA expressions of α-smooth muscle actin (αSMA) and type 1 and type 3 collagens and lowered expression of e-cadherin mRNA in PMCs compared to bicarbonate/lactate PDF. Lactate stimulation increased mRNA expressions of αSMA, matrix metalloproteinase 2 (MMP2), and basic fibroblast growth factor (bFGF) and suppressed e-cadherin mRNA expression. Transforming growth factor (TGF)-β1 and TGF-β2 and collagen type 1 and 3 mRNA expressions were also enhanced by lactate stimulation. Conclusions These results suggest that lactate as a PDF buffer may act on PMCs to promote epithelial-mesenchymal transition (EMT) and production of TGF-β, bFGF, and collagen.

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“…To clarify the downstream pathway of FOXD1, KEGG analysis was performed using co-expression genes (top 200) of FOXD1 found in the GEPIA database, and the results showed that FOXD1 was associated with glycolysis (data not shown). Among multiple glycolysis-related genes found in the GEPIA and ChIPBase databases, we found that FOXD1 has a strong positive association with lactate dehydrogenase A (LDHA), pyruvate kinase M2 (PKM) and enolase 1 (ENO1) genes (Fig 5H and Fig S2B-D), which play vital role in glycolysis [20][21][22]. The protein levels of LDHA, PKM, and ENO1 signi cantly decreased after FOXD1 knockdown, whereas the levels increased under FOXD1 overexpression (Fig 5J).…”

Section: Foxd1 Promotes the Glycolytic Level Of Npc Cellsmentioning

confidence: 98%

Long Non-Coding RNA FOXD1-AS1 Promotes the Progression and Glycolysis of Nasopharyngeal Carcinoma by Sustaining FOXD1 Expression

Wang

Cheng

Zhu

et al. 2020

Preprint

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Background: Increasing evidence have emphasized the importance of long non-coding RNAs (lncRNAs) in various human cancers progression. Forkhead box D1 antisense RNA1 (FOXD1-AS1) is a novel lncRNA and plays vital regulatory role in diverse biological processes of cancers. However, the biological function, molecular mechanism and clinical significance of FOXD1-AS1 in nasopharyngeal carcinoma is still unknown.Methods: Comprehensive bioinformatics analysis and qRT-PCR was conducted to detect the expression level of FOXD1-AS1. Loss-of-function and gain-of-function experiments were performed to verify the functions of FOXD1-AS1 in proliferation, migration, invasion, apoptosis and glycolysis of nasopharyngeal carcinoma in vitro and in vivo. Further bioinformatics analysis and experiments were carried out to explore the underlying molecular mechanisms of FOXD1-AS1. Results: FOXD1-AS1 was significantly overexpressed in nasopharyngeal carcinoma and associated with poor survival in patients. Knockdown of FOXD1-AS1 significantly inhibited cell proliferation, migration, invasion and glycolysis, and promotes apoptosis in nasopharyngeal carcinoma, whereas over-expression of FOXD1-AS1 has the opposite effect. Mechanistically, we found that FOXD1-AS1 could upregulate the expression of FOXD1 through stabilizing the FOXD1 expression at mRNA and protein levels, and FOXD1 increased the glycolysis level by transcriptionally upregulating the expression of LDHA, PKM and ENO1, thus playing an oncogenic role in nasopharyngeal carcinoma progression. Conclusion: FOXD1-AS1 plays a critical regulatory role in nasopharyngeal carcinoma. The identified FOXD1-AS1/FOXD1 axis may serve as a potential prognostic biomarker and therapeutic target for patients with nasopharyngeal carcinoma.

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LDHA Promotes Oral Squamous Cell Carcinoma Progression Through Facilitating Glycolysis and Epithelial–Mesenchymal Transition

Cited by 79 publications

References 45 publications

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer

Effect of lactate as a peritoneal dialysis fluid buffer on rat peritoneal mesothelial cells

Long Non-Coding RNA FOXD1-AS1 Promotes the Progression and Glycolysis of Nasopharyngeal Carcinoma by Sustaining FOXD1 Expression

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