Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells

Chen, Fei; Chen, Jianing; Yang, Lixuan; Liu, Jiang; Zhang, Xiaoqian; Zhang, Yin; Tu, Qingqiang; Ding, Yin; Lin, De–Chen; Wong, Ping-Pui; Huang, Di; Xing, Yue; Zhao, Jinghua; Li, Mengfeng; Liu, Qiang; Su, Fengxi; Su, Shicheng; Song, Erwei

doi:10.1038/s41556-019-0299-0

Cited by 514 publications

(368 citation statements)

References 51 publications

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“…Additionally, the phenomena that exosomes being delivered from immune cells to tumor cells or other kinds of immune cells are observed. On the one hand, TAMs strengthen the aerobic glycolysis and apoptotic resistance of breast cancer cells through the transmission of extracellular vesicles (EVs) with myeloid-specific lncRNA (40). Meanwhile, the exhausted CD8 + T cells, which express TIM-3 and PD-1 during the antitumor immune responses, exhibit reduced proliferation and impaired anticancer activities.…”

Section: Features and Functional Modules Of Lncrnas In Tumor Immune Rmentioning

confidence: 99%

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Luo

Yang

et al. 2020

Front. Oncol.

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Section: Features and Functional Modules Of Lncrnas In Tumor Immune Rmentioning

confidence: 99%

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Luo

Yang

et al. 2020

Front. Oncol.

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“…Similarly, our research was focused on the exploration of how YAP1 regulated glycolysis in CRC. According to previous investigations and bioinformatics predictions, HIF1A could promote tumour glycolysis [45][46][47], and its promoter region might have a DNA binding motif for TEAD1, a transcription coactivator of YAP1. Furthermore, ChIP analysis proved that YAP1/TEAD1 could co-regulate the transcription of HIF1A and further promote tumour glycolysis.…”

Section: Discussionmentioning

confidence: 95%

MiR-103a-3p promotes tumour glycolysis in colorectal cancer via Hippo/YAP1/HIF1A axis

Sun

Zhang

Yuan

et al. 2020

Preprint

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Background Glycolysis plays an essential role in the growth and metastasis of solid cancer and has received increasing attention in recent years. However, the complex regulatory mechanisms of tumour glycolysis remain elusive. This study aimed to explore the molecular effect and mechanism of the noncoding RNA miR-103a-3p on glycolysis in colorectal cancer (CRC). Methods We explored the effects of miR-103a-3p on glycolysis and the biological functions of CRC cells in vitro and in vivo. Furthermore, we investigated whether miR-103a-3p regulates HIF1A expression through the Hippo/YAP1 pathway, and evaluated the role of the miR-103a-3p-LATS2/SAV1-YAP1-HIF1A axis in promoting glycolysis and angiogenesis in CRC cells and contributing to invasion and metastasis of CRC cells. Results We found that miR-103a-3p is highly expressed in CRC tissues and cell lines compared with matched controls and the high expression of miR-103a-3p is associated with poor patient prognosis. Under hypoxic conditions, a high level of miR-103a-3p can promote the proliferation, invasion, migration, angiogenesis and glycolysis of CRC cells. Moreover, miR-103a-3p knockdown inhibits the growth, proliferation, and glycolysis of CRC cells and promotes the Hippo-YAP signalling pathway in nude mice in a xenograft model. Here, we demonstrated that miR-103a-3p could directly target LATS2 and SAV1. Subsequently, we verified that TEAD1, a transcriptional coactivator of Yes-associated protein 1 (YAP1), directly binds to the HIF1A promoter region and the YAP1 and TEAD1 proteins could co-regulate the expression of HIF1A, thus promoting tumour glycolysis. Conclusions MiR-103a-3p, which is highly expressed in CRC cells, promotes HIF1A expression by targeting the core molecules LATS2 and SAV1 of the Hippo/YAP1 pathway, contributing to enhanced proliferation, invasion, migration, glycolysis and angiogenesis in CRC. Our study revealed the functional mechanisms of miR-103a-3p/YAP1/HIF1A axis in CRC glycolysis, which would provide potential intervention targets for molecular targeted therapy of CRC.

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“…It has been reported that HIFα enhanced glycolysis through promoting the transcription of key glycolytic genes (Chen et al , 2019; Jia et al , 2019; Zhou et al , 2018). We hypothesized that whether SETD1A cooperated with HIF1α to enhance glycolysis.…”

Section: Resultsmentioning

confidence: 99%

Histone methyltransferase SETD1A interacts with HIF1α to enhance glycolysis and promote cancer progression in gastric cancer

Chai

et al. 2020

Molecular Oncology

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Growing tumors alter their metabolic profiles to support the increased cell proliferation. SETD1A, a histone lysine methyltransferase which specifically methylates H3K4, plays important roles in both normal cell and cancer cell functions. However, the function of SETD1A in gastric cancer (GC) progression and its role in GC metabolic reprogramming are still largely unknown. In the current study, we discovered that the expression of SETD1A was higher in GC tumor specimens compared to surrounding nontumor tissues. Upregulation of SETD1A increased GC cell proliferation, whereas downregulation of SETD1A inhibited GC cell proliferation. Furthermore, knockdown of SETD1A reduced glucose uptake and production of lactate and suppressed glycolysis by decreasing the expression of glycolytic genes, including GLUT1, HK2, PFK2, PKM2, LDHA, and MCT4. Mechanistically, SETD1A interacted with HIF1a to strengthen its transactivation, indicating that SETD1A promotes glycolysis through coactivation of HIF1a. SETD1A and HIF1a were recruited to the promoter of HK2 and PFK2, where SETD1A could methylate H3K4. However, knockdown of SETD1A decreased the methylation of H3K4 on HK2 and PFK2 promoter and reduced HIF1a recruitment necessary to promote transcription of glycolytic genes. Inhibition of HIF1a decelerated SETD1Aenhanced GC cell growth. In additional, there was a linear correlation between SETD1A and several key glycolytic genes in human GC specimens obtained from TCGA dataset. Thus, our results demonstrated that SETD1A interacted with HIF1a to promote glycolysis and accelerate GC progression, implicating that SETD1A may be a potential molecular target for GC treatment.

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Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells

Cited by 514 publications

References 51 publications

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

MiR-103a-3p promotes tumour glycolysis in colorectal cancer via Hippo/YAP1/HIF1A axis

Histone methyltransferase SETD1A interacts with HIF1α to enhance glycolysis and promote cancer progression in gastric cancer

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