Pigment epithelium-derived factor has a role in the progression of papillary thyroid carcinoma by affecting the HIF1α-VEGF signaling pathway

Lv, Yichen; Sun, Yu; Shi, Tiefeng; Shi, Chao; Qin, Huadong; Li, Zhaozhu

doi:10.3892/ol.2016.5316

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…VEGF recruits new microvessels that allow the delivery of nutrients and expansion of the tumor mass. Some previous studies have indicated that VEGF as a risk factor of developing PTC or tumor progression ( 79 , 80 ).…”

Section: Thyroid Cancer and Metabolismmentioning

confidence: 99%

Metabolic Reprogramming in Thyroid Carcinoma

2018

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Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer.

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Section: Thyroid Cancer and Metabolismmentioning

confidence: 99%

Metabolic Reprogramming in Thyroid Carcinoma

2018

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“…It has been reported that hypoxia-induced overexpression of HIF1α promotes epithelial–mesenchymal transition in FTC 5. Moreover, pigment epithelium-derived factor exhibits an antiangiogenesis role in FTC by affecting the HIF1α/VEGF pathway, eventually inhibits FTC metastasis and progression 6. These findings attach much significance to HIF1α expression on FTC development, while the correlation between HIF1α expression level and FTC clinicopathologic characteristics and its effect on cell apoptosis remain unclear.…”

Section: Introductionmentioning

confidence: 99%

<p>HIF1α/PD-L1 axis mediates hypoxia-induced cell apoptosis and tumor progression in follicular thyroid carcinoma</p>

Zhou

Cha²,

Chen

et al. 2019

OTT

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Background Hypoxia-inducible factor 1α (HIF-1α) and programmed cell death-1 protein ligand 1 (PD-L1) are implicated in the metastasis and progression processes of multiple cancers. Hypoxia selectively elevates PD-L1 expression via HIF1α activation in several solid tumors; however, the regulatory effect of HIF1α on PD-L1 in the pathogenesis of follicular thyroid cancer (FTC) remains unclear. This study aims to investigate the regulatory effect of HIF1α on PD-L1 and their potential roles in FTC pathogenesis. Methods Spearman correlation analysis was performed to clarify the relationships between HIF1α and PD-L1 expressions and the clinicopathologic characteristics. The expressions of HIF1α and PD-L1 at mRNA and protein levels were analyzed by qRT-PCR and Western blot. Hypoxia induction and cell transfection were conducted in FTC cells. TUNEL and Annexin V staining were used to detect the cell apoptosis. FTC xenograft tumor models were generated to evaluate the roles of HIF1α and PD-L1 in vivo. Results Here, we found that the expressions of HIF1α and PD-L1 were significantly increased in FTC tissues and were correlated with the FTC clinicopathologic features, such as the tumor size, T stage, TNM staging, and metastasis. In FTC cells, hypoxia-induced increased HIF1α and PD-L1 expression. Knockdown of HIF1α inhibits hypoxia-induced PD-L1 expression and cells apoptosis. Moreover, inhibition of HIF1α or PD-L1 significantly delays tumor growth and metastasis in vivo. Conclusion Hypoxia could promote FTC progression by upregulating HIF1α and PD-L1, which could serve as the molecular targets for FTC treatment.

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“… 36 Previous molecular investigations have lined the development of thyroid cancer with an array of consistent abnormalities in pathways such as HIF1α-VEGF, which together orchestrate tumor growth and angiogenesis. 37 MLL3 acts as an H3K4me1 methylase, 18 which could modulate the enhancer activity of DACT2 and the expression of DACT2. 18 , 19 In addition, we uncovered that inhibited expression of DACT2 resulted in the upregulation of YAP, which is consistent with the findings of a previous study in glioma.…”

Section: Discussionmentioning

confidence: 99%

miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis

Wang

Cen

Yang

et al. 2021

Molecular Therapy - Nucleic Acids

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Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, and angiogenesis plays critical roles in its recurrence and metastasis. In this study, we investigated the effects of hypoxia-induced exosomal microRNA-181 (miR-181a) from PTC on tumor growth and angiogenesis. Thyroid-cancer-related differentially expressed miR-181a was identified by microarray-based analysis in the Gene Expression Omnibus (GEO) database. We validated that miR-181a was highly expressed in PTC cells and even more so in cells cultured under hypoxic conditions, which also augmented exosome secretion from PTC cells. Exosomes extracted from PTC cells with manipulated miR-181a and mixed-lineage leukemia 3 (MLL3) were subjected to normoxic or hypoxic conditions. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-181a inhibitor/mimic or small interfering RNA (siRNA)-MLL3 or treated with exosomes from hypoxic PTC cells. Hypoxic exosomal miR-181a delivery promoted proliferation and capillary-like network formation in HUVECs. Mechanistically, miR-181a targeted and inhibited MLL3. Furthermore, miR-181a downregulated DACT2 and upregulated YAP and vascular endothelial growth factor (VEGF). Further, hypoxic exosomal miR-181a induced angiogenesis and tumor growth in vivo , which was reversed by hypoxic exosomal miR-181a inhibitor. In conclusion, exosomal miR-181a from hypoxic PTC cells promotes tumor angiogenesis and growth through MLL3 and DACT2 downregulation, as well as VEGF upregulation.

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Pigment epithelium-derived factor has a role in the progression of papillary thyroid carcinoma by affecting the HIF1α-VEGF signaling pathway

Cited by 9 publications

References 35 publications

Metabolic Reprogramming in Thyroid Carcinoma

Metabolic Reprogramming in Thyroid Carcinoma

<p>HIF1α/PD-L1 axis mediates hypoxia-induced cell apoptosis and tumor progression in follicular thyroid carcinoma</p>

miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis

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