Let-7a-5p inhibits triple-negative breast tumor growth and metastasis through GLUT12-mediated warburg effect

Shi, Yajiao; Zhang, Yanan; Ran, Fang; Liu, Jie; Lin, Jing; Hao, Xiaopeng; Ding, Lihua; Ye, Qinong

doi:10.1016/j.canlet.2020.09.012

Cited by 48 publications

(40 citation statements)

References 30 publications

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“…Overexpression of GLUT12 in breast and prostate cancer is associated with cancer development and characteristic glycolytic metabolism observed in malignant cells (55,58,59). This effect may be mediated through P53, estradiol and epidermal growth factor (56,60). GLUT12 could serve as a new therapeutic target due to its targeted expression on cancer cells.…”

Section: Key Process Of Glycolysismentioning

confidence: 99%

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The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer

2021

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Although chemotherapy can improve the overall survival and prognosis of cancer patients, chemoresistance remains an obstacle due to the diversity, heterogeneity, and adaptability to environmental alters in clinic. To determine more possibilities for cancer therapy, recent studies have begun to explore changes in the metabolism, especially glycolysis. The Warburg effect is a hallmark of cancer that refers to the preference of cancer cells to metabolize glucose anaerobically rather than aerobically, even under normoxia, which contributes to chemoresistance. However, the association between glycolysis and chemoresistance and molecular mechanisms of glycolysis-induced chemoresistance remains unclear. This review describes the mechanism of glycolysis-induced chemoresistance from the aspects of glycolysis process, signaling pathways, tumor microenvironment, and their interactions. The understanding of how glycolysis induces chemoresistance may provide new molecular targets and concepts for cancer therapy.

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Section: Key Process Of Glycolysismentioning

confidence: 99%

“…GLUT12 could serve as a new therapeutic target due to its targeted expression on cancer cells. For example, microRNA let-7a-5p (miR let-7a-5p) inhibits the proliferation, migration, and invasion of triple-negative breast cancer via GLUT12 inhibition (60).…”

Section: Key Process Of Glycolysismentioning

confidence: 99%

The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer

2021

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“…The GLUT expression showed a difference according to the metastatic sites, and the expression of GLUT1 was the highest in brain metastasis ( Kim H. M. et al, 2014 ). Additionally, GLUT12 plays an important role in tumor growth and metastasis through aerobic glycolysis in TNBC ( Shi et al, 2020 ).…”

Section: Impact Of Glucose Metabolism and Glucose Transporters On Breast Cancer Biology And The Response To Treatmentmentioning

confidence: 99%

Glucose Metabolism and Glucose Transporters in Breast Cancer

Shin

Koo

2021

Front. Cell Dev. Biol.

103

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Breast cancer is the most common malignancy in women worldwide and is associated with high mortality rates despite the continuously advancing treatment strategies. Glucose is essential for cancer cell metabolism owing to the Warburg effect. During the process of glucose metabolism, various glycolytic metabolites, such as serine and glycine metabolites, are produced and other metabolic pathways, such as the pentose phosphate pathway (PPP), are associated with the process. Glucose is transported into the cell by glucose transporters, such as GLUT. Breast cancer shows high expressions of glucose metabolism-related enzymes and GLUT, which are also related to breast cancer prognosis. Triple negative breast cancer (TNBC), which is a high-grade breast cancer, is especially dependent on glucose metabolism. Breast cancer also harbors various stromal cells such as cancer-associated fibroblasts and immune cells as tumor microenvironment, and there exists a metabolic interaction between these stromal cells and breast cancer cells as explained by the reverse Warburg effect. Breast cancer is heterogeneous, and, consequently, its metabolic status is also diverse, which is especially affected by the molecular subtype, progression stage, and metastatic site. In this review, we will focus on glucose metabolism and glucose transporters in breast cancer, and we will additionally discuss their potential applications as cancer imaging tracers and treatment targets.

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“…In contrast, identifying circRNAs’ regulatory molecules allows for the identification of their physiological roles. For example, microRNA let-7a-5p targets GLUT12 to regulate TNBC cells’ ATP generation, glucose uptake, lactate production, ECAR, and oxygen-consumption rate [ 27 ]. MiR-210-3p targets GPD1L to maintain the stabilization of HIF-1α and inhibits the activity of p53 through CYGB [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

CircRNA circ-PDCD11 promotes triple-negative breast cancer progression via enhancing aerobic glycolysis

Xing

Wang

et al. 2021

Cell Death Discov.

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Well-described evidence has demonstrated the critical roles of aerobic glycolysis in triple-negative breast cancer (TNBC) oncotherapy. Moreover, next-generation high-throughput sequencing indicates the potential regulation of energy metabolism by circular RNAs (circRNAs) in TNBC. However, circRNA modulation of TNBC aerobic glycolysis is still unclear. Here, the present research aimed to investigate the function and underlying mechanisms of novel circPDCD11 (hsa_circ_0019853) in TNBC aerobic glycolysis. The results revealed that circPDCD11 expression was significantly upregulated in TNBC tissues and cells. Clinical data demonstrated that the high expression of circPDCD11 was closely correlated with a poor prognosis and acted as an independent risk factor for TNBC prognosis. Functionally, in vitro gain- and loss-of-function experiments revealed that circPDCD11 accelerated glucose uptake, lactate production, ATP generation, and the extracellular acidification rate in TNBC cells. In vivo, circPDCD11 silencing repressed tumor growth. Mechanistically, circPDCD11 acted as a miRNA sponge to enhance LDHA expression by sponging miR-432-5p. In conclusion, these combined results demonstrated that circPDCD11 acts as an oncogene for TNBC, providing a promising prognostic biomarker for TNBC.

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Let-7a-5p inhibits triple-negative breast tumor growth and metastasis through GLUT12-mediated warburg effect

Cited by 48 publications

References 30 publications

The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer

The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer

Glucose Metabolism and Glucose Transporters in Breast Cancer

CircRNA circ-PDCD11 promotes triple-negative breast cancer progression via enhancing aerobic glycolysis

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