Mitochondrial dysfunction, UPRmt signaling, and targeted therapy in metastasis tumor

Keerthiga, Rajendiran; Pei, De‐Sheng; Fu, Ailing

doi:10.1186/s13578-021-00696-0

Cited by 23 publications

(10 citation statements)

References 157 publications

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“…The increased levels of ROS that are often present in cancer can lead to retrograde signaling through the JNK–PGC1-α pathway with increased complex II phosphorylation and enhancement of mitochondrial biogenesis [ 109 , 110 ]. As described above, PGAM5 is of great importance in several facets of mitochondrial function.…”

Section: Part 2: Emerging Evidence Of the Interplay Between Nrf2 And ...mentioning

confidence: 99%

NRF2 and Mitochondrial Function in Cancer and Cancer Stem Cells

Panieri

Pinho

Afonso

et al. 2022

Cells

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The NRF2–KEAP1 system is a fundamental component of the cellular response that controls a great variety of transcriptional targets that are mainly involved in the regulation of redox homeostasis and multiple cytoprotective mechanisms that confer adaptation to the stress conditions. The pleiotropic response orchestrated by NRF2 is particularly relevant in the context of oncogenic activation, wherein this transcription factor acts as a key driver of tumor progression and cancer cells’ resistance to treatment. For this reason, NRF2 has emerged as a promising therapeutic target in cancer cells, stimulating extensive research aimed at the identification of natural, as well as chemical, NRF2 inhibitors. Excitingly, the influence of NRF2 on cancer cells’ biology extends far beyond its mere antioxidant function and rather encompasses a functional crosstalk with the mitochondrial network that can influence crucial aspects of mitochondrial homeostasis, including biogenesis, oxidative phosphorylation, metabolic reprogramming, and mitophagy. In the present review, we summarize the current knowledge of the reciprocal interrelation between NRF2 and mitochondria, with a focus on malignant tumors and cancer stem cells.

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Section: Part 2: Emerging Evidence Of the Interplay Between Nrf2 And ...mentioning

confidence: 99%

NRF2 and Mitochondrial Function in Cancer and Cancer Stem Cells

Panieri

Pinho

Afonso

et al. 2022

Cells

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“…A few studies have indicated that PINK1 and Parkin are also activated upon accumulation of misfolded proteins in the mitochondrial lumen ( Burbulla et al, 2014 ; Fiesel et al, 2017 ). Here, we used mitochondrial chaperone Hsp60 as the mtUPR biomarker ( Keerthiga et al, 2021 ; Zhou et al, 2021 ) and found that the simulated microgravity did not show a much significant effect on the mRNA expression of Hsp60 ( Supplementary Figure S3 ). The result presented here supported that clinorotation activated PINK1 and induced mitophagy independently of mitochondrial-unfolded protein response.…”

Section: Resultsmentioning

confidence: 99%

PINK1-Dependent Mitophagy Reduced Endothelial Hyperpermeability and Cell Migration Capacity Under Simulated Microgravity

Pan

Tan

et al. 2022

Front. Cell Dev. Biol.

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The effect of cardiovascular dysfunction including orthostatic intolerance and disability on physical exercise is one of the health problems induced by long-term spaceflight astronauts face. As an important part of vascular structure, the vascular endothelium, uniquely sensitive to mechanical force, plays a pivotal role in coordinating vascular functions. Our study found that simulated microgravity induced PINK1-dependent mitophagy in human umbilical vein endothelial cells (HUVECs). Here, we explored the underlying mechanism of mitophagy induction. The ER stress induced by proteostasis failure in HUVECs promoted the Ca2+ transfer from ER to mitochondria, resulting in mitochondria Ca2+ overload, decreased mitochondrial membrane potential, mitochondria fission, and accumulation of Parkin and p62 in mitochondria and mitophagy under simulated microgravity. Moreover, we assumed that mitophagy played a vital role in functional changes in endothelial cells under simulated microgravity. Using mdivi-1 and PINK1 knockdown, we found that NLRP3 inflammasome activation was enhanced after mitophagy was inhibited. The NLRP3 inflammasome contributed to endothelial hyperpermeability and cellular migration by releasing IL-1β. Thus, mitophagy inhibited cell migration ability and hyperpermeability in HUVECs exposed to clinostat-simulated microgravity. Collectively, we here clarify the mechanism of mitophagy induction by simulated microgravity in vitro and demonstrate the relationship between mitophagy and vascular endothelial functional changes including cellular migration and permeability. This study deepens the understanding of vascular functional changes under microgravity.

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“… 54 Mitochondria dysfunction has also been verified as another vital factor in tumor proliferation and metastasis, and targeted drugs for certain mitochondria processes are regarded as promising strategies for patients with metastatic tumors. 55 , 56 , 57 Summarily, we assumed that the selected SNORD1A co‐expressed genes might play crucial roles in DLBCL progression by influencing ribosomal and mitochondrial processes.…”

Section: Discussionmentioning

confidence: 99%

Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B‐cell lymphoma

Huang

Xie

et al. 2022

Cancer Medicine

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Background Diffuse large B‐cell lymphoma (DLBCL) is a non‐Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor‐specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Materials and Methods Survival‐related snoRNAs were selected to construct a specific snoRNA‐based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein–protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co‐expressed genes. Results Twelve prognosis‐correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three‐snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high‐risk and low‐risk cohorts using the risk model, and the high‐risk group and activated B cell‐like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co‐expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co‐expressed genes in DLBCL. Conclusion Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.

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Mitochondrial dysfunction, UPRmt signaling, and targeted therapy in metastasis tumor

Cited by 23 publications

References 157 publications

NRF2 and Mitochondrial Function in Cancer and Cancer Stem Cells

NRF2 and Mitochondrial Function in Cancer and Cancer Stem Cells

PINK1-Dependent Mitophagy Reduced Endothelial Hyperpermeability and Cell Migration Capacity Under Simulated Microgravity

Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B‐cell lymphoma

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