A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer

Du, Ye; Wei, Na; Ma, Ruolin; Jiang, Shu‐Heng; Song, Dong Eun

doi:10.1038/s41419-020-02952-6

Cited by 77 publications

(59 citation statements)

References 38 publications

(46 reference statements)

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“…It has been shown that cancer cells prefer glycolysis as their energy source instead of OXPHOS, even in the presence of oxygen. Certain molecules like HIFs are essential to the survival of cancer cells in a hypoxic environment as transcriptional regulators of aerobic glycolysis 42 , 43 . The activation of HIFs in cancer can cause complex reprogramming of energy metabolism, including mitochondrial oxidative metabolism, glucose catabolism, glucose uptake, and energy production 18 .…”

Section: Role Of Hifs In Tumor Progressionmentioning

confidence: 99%

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

et al. 2021

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Mitochondria are essential cellular organelles that are involved in regulating cellular energy, metabolism, survival, and proliferation. To some extent, cancer is a genetic and metabolic disease that is closely associated with mitochondrial dysfunction. Hypoxia-inducible factors (HIFs), which are major molecules that respond to hypoxia, play important roles in cancer development by participating in multiple processes, such as metabolism, proliferation, and angiogenesis. The Warburg phenomenon reflects a pseudo-hypoxic state that activates HIF-1α. In addition, a product of the Warburg effect, lactate, also induces HIF-1α. However, Warburg proposed that aerobic glycolysis occurs due to a defect in mitochondria. Moreover, both HIFs and mitochondrial dysfunction can lead to complex reprogramming of energy metabolism, including reduced mitochondrial oxidative metabolism, increased glucose uptake, and enhanced anaerobic glycolysis. Thus, there may be a connection between HIFs and mitochondrial dysfunction. In this review, we systematically discuss the crosstalk between HIFs and mitochondrial dysfunctions in cancer development. Above all, the stability and activity of HIFs are closely influenced by mitochondrial dysfunction related to tricarboxylic acid cycle, electron transport chain components, mitochondrial respiration, and mitochondrial-related proteins. Furthermore, activation of HIFs can lead to mitochondrial dysfunction by affecting multiple mitochondrial functions, including mitochondrial oxidative capacity, biogenesis, apoptosis, fission, and autophagy. In general, the regulation of tumorigenesis and development by HIFs and mitochondrial dysfunction are part of an extensive and cooperative network.

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Section: Role Of Hifs In Tumor Progressionmentioning

confidence: 99%

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

et al. 2021

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“…When comparing the remaining potential miRNAs, according to the present bioinformatics analysis (miR-93-5p, miR-23c, miR-210-3p, miR-221-3p, and miR-592), all were suggested with important roles in PC screening [61], aggressiveness [8,62,63], and recurrence [7,18,64], or even new etiological values [65] were suggested. These miRNAs have also been highlighted with carcinogenic effects in other tumors, such as endometrial [66,67], osteosarcoma [68], hepatocellular [69], renal [17,70], or colorectal [71], among others [72][73][74]. According to our experimental analysis, miR-210-3p, miR-23c, and miR-592 were suggested as aggressiveness biomarkers in PC and miR-93-5p, miR-130b, and miR-141 were suggested as diagnostic biomarkers for this tumor.…”

Section: Discussionmentioning

confidence: 62%

Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer

et al. 2021

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MiRNAs play a relevant role in PC (prostate cancer) by the regulation in the expression of several pathways’ AR (androgen receptor), cellular cycle, apoptosis, MET (mesenchymal epithelium transition), or metastasis. Here, we report the role of several miRNAs’ expression patterns, such as miR-miR-93-5p, miR-23c, miR-210-3p, miR-221-3p, miR-592, miR-141, miR-375, and miR-130b, with relevance in processes like cell proliferation and MET. Using Trizol® extraction protocol and TaqMan™ specific probes for amplification, we performed miRNAs’ analysis of 159 PC fresh tissues and 60 plasmas from peripheral blood samples. We had clinical data from all samples including PSA, Gleason, TNM, and D’Amico risk. Moreover, a bioinformatic analysis in TCGA (The Cancer Genome Atlas) was included to analyze the effect of the most relevant miRNAs according to aggressiveness in an extensive cohort (n = 531). We found that miR-210-3p, miR-23c, miR-592, and miR-93-5p are the most suitable biomarkers for PC aggressiveness and diagnosis, respectively. In fact, according with our results, miR93-5p seems the most promising non-invasive biomarker for PC. To sum up, miR-210-3p, miR-23c, miR-592, and miR93-5p miRNAs are suggested to be potential biomarkers for PC risk stratification that could be included in non-invasive strategies such as liquid biopsy in precision medicine for PC management.

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“…It was demonstrated that miR-210 targets the electron transport chain through SDHD (succinate dehydrogenase complex, subunit D), inducing accumulation of succinate that, in turn, inhibits Prolyl hydroxylase domain enzymes (PHD) and stabilizes HIF-1α, thus forming a positive-autoregulatory loop [ 125 ]. More recently, Du et al demonstrated that miR-210-3p targets GPD1L (glycerol-3-phosphate dehydrogenase 1-like) and consequently affects HIF1α stability inducing an effect similar to that observed with SDHD inhibition [ 61 ].…”

Section: Feedback Loops Between Hif and The Hypoxia-induced Non-comentioning

confidence: 98%

“…Recently, an interesting manuscript of Du et al demonstrated that hypoxia-induced miR-210-3p controls cell proliferation by promoting Warburg effects and, concomitantly by inhibiting p53 activity in triple-negative breast cancer [ 61 ].…”

Section: The Hypoxia-induced Non-coding Rnasmentioning

confidence: 99%

Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer

Barreca

Zichittella

Alessandro

et al. 2021

IJMS

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Hypoxia, a characteristic of the tumour microenvironment, plays a crucial role in cancer progression and therapeutic response. The hypoxia-inducible factors (HIF-1α, HIF-2α, and HIF-3α), are the master regulators in response to low oxygen partial pressure, modulating hypoxic gene expression and signalling transduction pathways. HIFs’ activation is sufficient to change the cell phenotype at multiple levels, by modulating several biological activities from metabolism to the cell cycle and providing the cell with new characteristics that make it more aggressive. In the past few decades, growing numbers of studies have revealed the importance of non-coding RNAs (ncRNAs) as molecular mediators in the establishment of hypoxic response, playing important roles in regulating hypoxic gene expression at the transcriptional, post-transcriptional, translational, and posttranslational levels. Here, we review recent findings on the different roles of hypoxia-induced ncRNAs in cancer focusing on the data that revealed their involvement in tumour growth.

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A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer

Cited by 77 publications

References 38 publications

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

The crosstalk between HIFs and mitochondrial dysfunctions in cancer development

Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer

Hypoxia-Induced Non-Coding RNAs Controlling Cell Viability in Cancer

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