miR-200b is a key regulator of tumor progression and metabolism targeting lactate dehydrogenase A in human malignant glioma

Hu, Su; Jiang, Qian; Luo, Dan; Zhao, Lei; Fu, Xin; Chen, Yuqin; Song, Xue; Li, Lihua; Zhao, Hailin; He, Yong; Peng, Bingwei

doi:10.18632/oncotarget.10301

Cited by 32 publications

(17 citation statements)

References 37 publications

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“…In the present study, we have demonstrated that miR‐200b‐3p and miR‐200c‐3p have significantly reduced expression in GBM tissues and that their downregulation is negatively correlated with HMGB3 overexpression. Dysregulation of miR‐200 family members occurs in a variety of cancers, including in GBM where miR‐200b was shown to negatively regulate tumour progression and metabolism by targeting lactate dehydrogenase A . That the miR‐200 family members tend to play a tumour‐suppressive role further substantiates our study's findings, which strongly suggest a tumour‐suppressive role for miR‐200b‐3p and miR‐200c‐3p through HMGB3 inhibition.…”

Section: Discussionsupporting

confidence: 84%

HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR‐200b‐3p and miR‐200c‐3p

Liu

Wang

2018

Cell Biochemistry & Function

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High mobility group box 3 (HMGB3) is strongly involved in oncogenesis in a variety of cancers. In the present study, we have explored the role of HMGB3 in glioblastoma multiforme (GBM) tumorigenesis and have identified the microRNAs (miRNAs) miR-200b-3p and miR-200c-3p as negative regulators of HMGB3 expression. We began by determining that endogenous HMGB3 expression levels were significantly elevated in GBM tissues and in 3 GBM cell lines. To study the function of HMGB3 in GBM, we transfected a small-interfering RNA (siRNA) against HMGB3 into GBM cell lines U251 and LN229. MTT and tumour sphere assays demonstrated that HMGB3 knockdown significantly inhibited cell proliferation. Wound healing and transwell assays determined that HMGB3 knockdown substantially suppressed GBM cell migration and invasion. We evaluated the effects of HMGB3 knockdown on MAPK phosphorylation and target gene expression, finding that HMGB3 knockdown significantly reduced MAPK phosphorylation (p-ERK (1/2), p-p38, and p-JNK). We then used the biologic prediction algorithm TargetScan to identify the 3' untranslated region (3'-UTR) of HMGB3 as a target of miR-200b-3p and miR-200c-3p. Luciferase, qRT-PCR, and western blot assays confirmed that miR-200b-3p and miR-200c-3p bind and inhibit HMGB3 expression. Finally, Pearson correlation analyses demonstrated a negative correlation between relative HMGB3 mRNA and miR-200b/c-3p expression levels in GBM tissue samples. Overall, the present study strongly suggests that HMGB3 promotes GBM oncogenesis through the MAPK signalling pathway while miR-200b-3p and miR-200c-3p inhibit its expression.

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Section: Discussionsupporting

confidence: 84%

HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR‐200b‐3p and miR‐200c‐3p

Liu

Wang

2018

Cell Biochemistry & Function

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“…Our research showed that miR-200b and miR-200c expression levels were decreased in breast cancer cells after exposure of hypoxia, uncovering that they might be associated with regulation of hypoxia. Previous studies demonstrated that miR-200b and miR-200c could inhibit glycolysis in cancers by targeting lactate dehydrogenase A and sirtuin 2 [30,31]. Additionally, miR-200b and miR-200c could suppress migration and invasion of breast cancer cells by regulating ezrin-radixin-moesin and fucosyltransferase-4 [32,33].…”

Section: Discussionmentioning

confidence: 99%

Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

Ren

Liu

Feng

et al. 2019

J Exp Clin Cancer Res

141

105

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Background: Hypoxia is a key feature of breast cancer, which affects cancer development, metastasis and metabolism. Previous studies suggested that circular RNAs (circRNAs) could participate in cancer progression and hypoxia regulation. This study aimed to investigate the role of circRNA differentially expressed in normal cells and neoplasia domain containing 4C (circDENND4C) in breast cancer progression under hypoxia. Methods: Forty-three patients with breast cancer were involved in this study. Breast cancer cell lines MDA-MB-453 and SK-BR-3 were cultured under hypoxia (1% O 2) for experiments in vitro. The expression levels of circDENND4C, microRNA-200b (miR-200b) and miR-200c were measured by quantitative real-time polymerase chain reaction. Glycolysis was investigated by glucose consumption, lactate production and hexokinase II (HK2) protein level. Migration and invasion were evaluated via trans-well assay and protein levels of matrix metallopeptidase 9 (MMP9) and MMP2. The interaction between circDENND4C and miR-200b or miR-200c was explored by bioinformatics analysis, luciferase assay and RNA immunoprecipitation. Murine xenograft model was established to investigate the anti-cancer role of circDENND4C in vivo. Results: circDENND4C highly expressed in breast cancer was up-regulated in response to hypoxia. Knockdown of circDENND4C decreased glycolysis, migration and invasion in breast cancer cells under hypoxia. circDENND4C was validated as a sponge of miR-200b and miR-200c. Deficiency of miR-200b or miR-200c reversed the suppressive effect of circDENND4C knockdown on breast cancer progression. Moreover, silence of circDENND4C reduced xenograft tumor growth by increasing miR-200b and miR-200c. Conclusion: circDENND4C silence suppresses glycolysis, migration and invasion in breast cancer cells under hypoxia by increasing miR-200b and miR-200c.

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“…MiR200b reduces iNOS expression and NO production and limits the migratory potential of reactive microglia. Suppression of the glycolytic enzyme lactate dehydrogenase A (LDHA) and aerobic glycolysis likely underlies the miRNA action (S. Hu et al, ); (Table ).…”

Section: Micrornas Promoting Pro‐regenerative Microglia Phenotype Andmentioning

confidence: 99%

How to reprogram microglia toward beneficial functions

Fumagalli

Lombardi

Gressèns

et al. 2018

Glia

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Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined. Here we review emerging strategies to drive microglia toward beneficial functions, selectively reporting the studies which provide insights into molecular mechanisms underlying the phenotypic switch. A variety of approaches have been proposed which rely on microglia treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs, as well on nutritional approaches or therapies with immunomodulatory cells. Analysis of the molecular mechanisms relevant for microglia reprogramming toward pro-regenerative functions points to a central role of energy metabolism in shaping microglial functions. Manipulation of metabolic pathways may thus provide new therapeutic opportunities to prevent the deleterious effects of inflammatory microglia and to control excessive inflammation in brain disorders.

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miR-200b is a key regulator of tumor progression and metabolism targeting lactate dehydrogenase A in human malignant glioma

Cited by 32 publications

References 37 publications

HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR‐200b‐3p and miR‐200c‐3p

HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR‐200b‐3p and miR‐200c‐3p

Knockdown of circDENND4C inhibits glycolysis, migration and invasion by up-regulating miR-200b/c in breast cancer under hypoxia

How to reprogram microglia toward beneficial functions

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