A review on interplay between small RNAs and oxidative stress in cancer progression

Aim. To investigate the function of Tremella fuciformis polysaccharides (TFPS) in LPS-induced inflammation and oxidative stress of macrophages. Methods. RAW264.7 cells were pretreated with TFPS and then stimulated with 0.1 μg/ml LPS. NFκB, Akt, p38MAPK, MCP-1, and SOD-1 were analyzed by Western blotting. Cell viability was measured using MTT assays. Reactive oxygen species (ROS) production, real-time PCR, ELISA, and immunofluorescence staining were performed on RAW264.7 cells that were treated with LPS and/or TFPS to investigate the anti-inflammatory effect of TFPS. Results. LPS induced inflammation and ROS production and promoted the secretion of cytokines such as TNF-α and IL-6. LPS also enhanced the nuclear translocation of NFκB, which promoted inflammation by oxidative stress. However, pretreatment with TFPS profoundly inhibited the activation of Akt, p38MAPK, and NFκB and attenuated the expression of MCP-1 in macrophages. Meanwhile, TFPS also decreased cytokine and ROS levels and attenuated cell inflammation after treatment with LPS. Moreover, miR-155, one of the key small RNAs which regulate NFκB and inflammation in macrophages, was significantly downregulated. Conclusion. TFPS inhibits LPS-induced oxidative stress and inflammation by inhibiting miR-155 expression and NFκB activation in macrophages, which suggests that TFPS may be a potential reagent for inhibiting the development of inflammation.

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TrxR1, Gsr, and oxidative stress determine hepatocellular carcinoma malignancy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1903244116 ◽

2019 ◽

Vol 116 (23) ◽

pp. 11408-11417 ◽

Cited By ~ 13

Author(s):

Michael R. McLoughlin ◽

David J. Orlicky ◽

Justin R. Prigge ◽

Pushya Krishna ◽

Emily A. Talago ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Standard Care ◽

Antioxidant Systems ◽

Null Mouse ◽

Dependent Manner ◽

Damage Indices ◽

And Oxidative Stress

Thioredoxin reductase-1 (TrxR1)-, glutathione reductase (Gsr)-, and Nrf2 transcription factor-driven antioxidant systems form an integrated network that combats potentially carcinogenic oxidative damage yet also protects cancer cells from oxidative death. Here we show that although unchallenged wild-type (WT), TrxR1-null, or Gsr-null mouse livers exhibited similarly low DNA damage indices, these were 100-fold higher in unchallenged TrxR1/Gsr–double-null livers. Notwithstanding, spontaneous cancer rates remained surprisingly low in TrxR1/Gsr-null livers. All genotypes, including TrxR1/Gsr-null, were susceptible to N-diethylnitrosamine (DEN)-induced liver cancer, indicating that loss of these antioxidant systems did not prevent cancer cell survival. Interestingly, however, following DEN treatment, TrxR1-null livers developed threefold fewer tumors compared with WT livers. Disruption of TrxR1 in a marked subset of DEN-initiated cancer cells had no effect on their subsequent contributions to tumors, suggesting that TrxR1-disruption does not affect cancer progression under normal care, but does decrease the frequency of DEN-induced cancer initiation. Consistent with this idea, TrxR1-null livers showed altered basal and DEN-exposed metabolomic profiles compared with WT livers. To examine how oxidative stress influenced cancer progression, we compared DEN-induced cancer malignancy under chronically low oxidative stress (TrxR1-null, standard care) vs. elevated oxidative stress (TrxR1/Gsr-null livers, standard care or phenobarbital-exposed TrxR1-null livers). In both cases, elevated oxidative stress was correlated with significantly increased malignancy. Finally, although TrxR1-null and TrxR1/Gsr-null livers showed strong Nrf2 activity in noncancerous hepatocytes, there was no correlation between malignancy and Nrf2 expression within tumors across genotypes. We conclude that TrxR1, Gsr, Nrf2, and oxidative stress are major determinants of liver cancer but in a complex, context-dependent manner.

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The in vitro effect of the diabetes-associated markers insulin, leptin and oxidative stress on cellular characteristics promoting breast cancer progression is GLUT1-dependent

European Journal of Pharmacology ◽

10.1016/j.ejphar.2021.173980 ◽

2021 ◽

pp. 173980

Author(s):

Cláudia Silva ◽

Nelson Andrade ◽

João Tiago Guimarães ◽

Emília Patrício ◽

Fátima Martel

Keyword(s):

Breast Cancer ◽

Oxidative Stress ◽

Cancer Progression ◽

Breast Cancer Progression ◽

Vitro Effect ◽

And Oxidative Stress

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Distinct stress-dependent signatures of cellular and extracellular tRNA-derived small RNAs (tDRs)

10.1101/2021.09.03.458085 ◽

2021 ◽

Author(s):

Guoping Li ◽

Aidan Manning ◽

Alex Bagi ◽

Xinyu Yang ◽

Jonathan Howard ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Responses ◽

Small Rnas ◽

Cellular Stress ◽

Fragmentation Pattern ◽

Cellular Models ◽

Nutritional Deprivation ◽

Cellular Stress Responses ◽

Stress Dependent ◽

And Oxidative Stress

The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may yield novel biomarkers for different diseases, and potentially identify key signaling pathways important for disease progression. tRNAs and tRNA-derived small RNAs (tDRs) comprise one of the most abundant RNA species in cells and have been associated with cellular stress responses. The presence of RNA modifications on tDRs has been an obstacle for accurately identifying tDRs with conventional small RNA sequencing. Here, we use AlkB-facilitated methylation sequencing (ARM-seq) to uncover a comprehensive landscape of cellular and extracellular tDR expression in a variety of human and rat cells during common stress responses, including nutritional deprivation, hypoxia, and oxidative stress. We found that extracellular tDRs have a distinct fragmentation signature with a predominant length of 31-33 nts and a highly specific termination position when compared with intracellular tDRs. Importantly, we found these signatures are better discriminators of different cellular stress responses compared to extracellular miRNAs. Distinct extracellular tDR signatures for each profiled stressor are elucidated in four different types of cells. This distinct extracellular tDR fragmentation pattern is also noted in plasma extracellular RNAs from patients on cardiopulmonary bypass. The observed overlap of these patient tDR signatures with the signatures of nutritional deprivation and oxidative stress in our cellular models provides preliminary in vivo corroboration of our findings and demonstrates the potential to establish novel extracellular tDR biomarkers in human disease models.

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Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer

Biomolecules ◽

10.3390/biom10010135 ◽

2020 ◽

Vol 10 (1) ◽

pp. 135 ◽

Cited By ~ 8

Author(s):

Rosario Avolio ◽

Danilo Swann Matassa ◽

Daniela Criscuolo ◽

Matteo Landriscina ◽

Franca Esposito

Keyword(s):

Oxidative Stress ◽

Cancer Cells ◽

Cancer Progression ◽

Tumor Biology ◽

Tumor Necrosis Factor Receptor ◽

Heat Shock Protein 90 ◽

Response To Therapy ◽

Metabolic Reprogramming ◽

Mitochondrial Activity ◽

And Oxidative Stress

Metabolic reprogramming, carried out by cancer cells to rapidly adapt to stress such as hypoxia and limited nutrient conditions, is an emerging concepts in tumor biology, and is now recognized as one of the hallmarks of cancer. In contrast with conventional views, based on the classical Warburg effect, these metabolic alterations require fully functional mitochondria and finely-tuned regulations of their activity. In turn, the reciprocal regulation of the metabolic adaptations of cancer cells and the microenvironment critically influence disease progression and response to therapy. This is also realized through the function of specific stress-adaptive proteins, which are able to relieve oxidative stress, inhibit apoptosis, and facilitate the switch between metabolic pathways. Among these, the molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1), the most abundant heat shock protein 90 (HSP90) family member in mitochondria, is particularly relevant because of its role as an oncogene or a tumor suppressor, depending on the metabolic features of the specific tumor. This review highlights the interplay between metabolic reprogramming and cancer progression, and the role of mitochondrial activity and oxidative stress in this setting, examining the possibility of targeting pathways of energy metabolism as a therapeutic strategy to overcome drug resistance, with particular emphasis on natural compounds and inhibitors of mitochondrial HSP90s.

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Transforming Growth Factor-Beta and Oxidative Stress Interplay: Implications in Tumorigenesis and Cancer Progression

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/654594 ◽

2015 ◽

Vol 2015 ◽

pp. 1-15 ◽

Cited By ~ 81

Author(s):

Jelena Krstić ◽

Drenka Trivanović ◽

Slavko Mojsilović ◽

Juan F. Santibanez

Keyword(s):

Oxidative Stress ◽

Growth Factor ◽

Cancer Progression ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Careful Consideration ◽

Cancer Therapies ◽

Antitumor Effects ◽

Growth Factor Beta ◽

And Oxidative Stress

Transforming growth factor-beta (TGF-β) and oxidative stress/Reactive Oxygen Species (ROS) both have pivotal roles in health and disease. In this review we are analyzing the interplay between TGF-βand ROS in tumorigenesis and cancer progression. They have contradictory roles in cancer progression since both can have antitumor effects, through the induction of cell death, senescence and cell cycle arrest, and protumor effects by contributing to cancer cell spreading, proliferation, survival, and metastasis. TGF-βcan control ROS production directly or by downregulating antioxidative systems. Meanwhile, ROS can influence TGF-βsignaling and increase its expression as well as its activation from the latent complex. This way, both are building a strong interplay which can be taken as an advantage by cancer cells in order to increment their malignancy. In addition, both TGF-βand ROS are able to induce cell senescence, which in one way protects damaged cells from neoplastic transformation but also may collaborate in cancer progression. The mutual collaboration of TGF-βand ROS in tumorigenesis is highly complex, and, due to their differential roles in tumor progression, careful consideration should be taken when thinking of combinatorial targeting in cancer therapies.

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Proteomics-Metabolomics Combined Approach Identifies Peroxidasin as a Protector against Metabolic and Oxidative Stress in Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20123046 ◽

2019 ◽

Vol 20 (12) ◽

pp. 3046 ◽

Cited By ~ 4

Author(s):

Dougan ◽

Hawsawi ◽

Burton ◽

Edwards ◽

Jones ◽

...

Keyword(s):

Oxidative Stress ◽

Prostate Cancer ◽

Cancer Progression ◽

Soft Agar ◽

Prostate Cancer Progression ◽

Nucleotide Biosynthesis ◽

Cardiovascular Tissue ◽

The Family ◽

Heme Peroxidases ◽

And Oxidative Stress

: Peroxidasin (PXDN), a human homolog of Drosophila PXDN, belongs to the family of heme peroxidases and has been found to promote oxidative stress in cardiovascular tissue, however, its role in prostate cancer has not been previously elucidated. We hypothesized that PXDN promotes prostate cancer progression via regulation of metabolic and oxidative stress pathways. We analyzed PXDN expression in prostate tissue by immunohistochemistry and found increased PXDN expression with prostate cancer progression as compared to normal tissue or cells. PXDN knockdown followed by proteomic analysis revealed an increase in oxidative stress, mitochondrial dysfunction and gluconeogenesis pathways. Additionally, Liquid Chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomics confirmed that PXDN knockdown induced global reprogramming associated with increased oxidative stress and decreased nucleotide biosynthesis. We further demonstrated that PXDN knockdown led to an increase in reactive oxygen species (ROS) associated with decreased cell viability and increased apoptosis. Finally, PXDN knockdown decreased colony formation on soft agar. Overall, the data suggest that PXDN promotes progression of prostate cancer by regulating the metabolome, more specifically, by inhibiting oxidative stress leading to decreased apoptosis. Therefore, PXDN may be a biomarker associated with prostate cancer and a potential therapeutic target.

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