Clinical Implications of Augmenter of Liver Regeneration in Cancer: A Systematic Review

Nguyen, Kevin; Nguyen, Austin Huy; Dabir, Deepa V.

doi:10.21873/anticanres.11704

Cited by 9 publications

(7 citation statements)

References 17 publications

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“…Particularly, a concisely reported upregulation of the DRS in HCC (Yu et al, 2014), focused our interest in the present study. However, previous studies on ALR rarely discriminated between its isoforms, the mainly cytosolic short form, and the predominantly mitochondrial long form (Nguyen et al, 2017). These two isoforms perform vastly different functions, making any results including non-isoform specific knockdown and overexpression hard to interpret.…”

Section: Discussionmentioning

confidence: 97%

“…Upregulation of the mitochondrial disulfide relay (DRS) in many different cancers makes it a promising potential target in cancer therapy (Nguyen et al, 2017). However, since knockouts of the DRS are lethal, this system needs to be targeted either by knockdown or chemical inhibition (Rissler et al, 2005).…”

Section: Mitoblock-6 Provokes Pronounced Proliferation Deficits In Hepatocellular Carcinoma Cellsmentioning

confidence: 99%

“…ALR passes these electrons to cytochrome C to feed them into the respiratory chain (Fischer and Riemer, 2013). Numerous studies point out that ALR is upregulated in HCC, suggesting a pivotal role of this relay system in this tumor type [reviewed in Nguyen et al (2017)]. ALR is an ubiquitously expressed protein with two main isoforms, a shorter 16 kD protein and a longer 23 kD protein which contains a mitochondrial targeting sequence.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation

Kabiri

Fuhrmann

Becker

et al. 2021

Front. Cell Dev. Biol.

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Augmenter of liver regeneration (ALR) is a critical multi-isoform protein with its longer isoform, located in the mitochondrial intermembrane space, being part of the mitochondrial disulfide relay system (DRS). Upregulation of ALR was observed in multiple forms of cancer, among them hepatocellular carcinoma (HCC). To shed light into ALR function in HCC, we used MitoBloCK-6 to pharmacologically inhibit ALR, resulting in profound mitochondrial impairment and cancer cell proliferation deficits. These effects were mostly reversed by supplementation with bioavailable hemin b, linking ALR function to mitochondrial iron homeostasis. Since many tumor cells are known for their increased iron demand and since increased iron levels in cancer are associated with poor clinical outcome, these results help to further advance the intricate relation between iron and mitochondrial homeostasis in liver cancer.

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Section: Discussionmentioning

confidence: 97%

Section: Mitoblock-6 Provokes Pronounced Proliferation Deficits In Hepatocellular Carcinoma Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation

Kabiri

Fuhrmann

Becker

et al. 2021

Front. Cell Dev. Biol.

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“…Moreover, in the first week of “N”, lower expression of BMP3 and BMP5 can derepress intestinal stem cells (ISC) in the crypt, therefore promoting intestinal regeneration. In week 4, genes which are highly expressed in “N”, including GFER, IL12A, and REG1A, play important roles in digestive organ regeneration, including GFER in liver regeneration [44], REG1A in pancreatic islet cells regeneration [45], and IL12A in antiangiogenesis [46]. On the contrary, in week 4 “A”, genes have functions related to mitosis, migration, and vasculogenesis (VEGFA) [47], maintaining and promoting connective tissue function and growth (PDGFC) [48].…”

Section: Discussionmentioning

confidence: 99%

Identifying the Growth Factors for Improving Neointestinal Regeneration in Rats through Transcriptome Analysis Using RNA-Seq Data

Jwo

Chung

Wang³

et al. 2018

BioMed Research International

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Using our novel surgical model of simultaneous intestinal adaptation “A” and neointestinal regeneration “N” conditions in individual rats to determine feasibility for research and clinical application, we further utilized next generation RNA sequencing (RNA-Seq) here in normal control tissue and both conditions (“A” and “N”) across time to decipher transcriptome changes in neoregeneration and adaptation of intestinal tissue at weeks 1, 4, and 12. We also performed bioinformatics analyses to identify key growth factors for improving intestinal adaptation and neointestinal regeneration. Our analyses indicate several interesting phenomena. First, Gene Ontology and pathway analyses indicate that cell cycle and DNA replication processes are enhanced in week 1 “A”; however, in week 1 “N”, many immune-related processes are involved. Second, we found some growth factors upregulated or downregulated especially in week 1 “N” versus “A”. Third, based on each condition and time point versus normal control tissue, we found in week 1 “N” BMP2, BMP3, and NTF3 are significantly and specifically downregulated, indicating that the regenerative process may be inhibited in the absence of these growth factors. This study reveals complex growth factor regulation in small neointestinal regeneration and intestinal adaptation and provides potential applications in tissue engineering by introducing key growth factors identified here into the injury site.

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“…On the other hand, MB-6 inhibits the sulfhydryl oxidase Erv1 and, in turn, Mia40 function in the import of intermembrane space proteins ( 180 , 181 ). Interestingly, the human homolog of Erv1 (ALR) is found upregulated in hepatocellular carcinoma cell lines and tissues, while its silencing or inhibition through MB-6 impairs mitochondrial function and inhibits the proliferation of liver cancer cells ( 157 , 182 ). MitoBloCKs can be a useful tool to study the role of mitochondrial translocation machinery in cancer, and the transcriptional and proteomic responses induced by accumulation of precursors in the cytosol, following the inhibition of protein import.…”

Section: Mitochondrial Translation-targeted Therapy In Human Cancersmentioning

confidence: 99%

Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy

et al. 2021

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Extensive metabolic remodeling is a fundamental feature of cancer cells. Although early reports attributed such remodeling to a loss of mitochondrial functions, it is now clear that mitochondria play central roles in cancer development and progression, from energy production to synthesis of macromolecules, from redox modulation to regulation of cell death. Biosynthetic pathways are also heavily affected by the metabolic rewiring, with protein synthesis dysregulation at the hearth of cellular transformation. Accumulating evidence in multiple organisms shows that the metabolic functions of mitochondria are tightly connected to protein synthesis, being assembly and activity of respiratory complexes highly dependent on de novo synthesis of their components. In turn, protein synthesis within the organelle is tightly connected with the cytosolic process. This implies an entire network of interactions and fine-tuned regulations that build up a completely under-estimated level of complexity. We are now only preliminarily beginning to reconstitute such regulatory level in human cells, and to perceive its role in diseases. Indeed, disruption or alterations of these connections trigger conditions of proteotoxic and energetic stress that could be potentially exploited for therapeutic purposes. In this review, we summarize the available literature on the coordinated regulation of mitochondrial and cytosolic mRNA translation, and their effects on the integrity of the mitochondrial proteome and functions. Finally, we highlight the potential held by this topic for future research directions and for the development of innovative therapeutic approaches.

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Clinical Implications of Augmenter of Liver Regeneration in Cancer: A Systematic Review

Cited by 9 publications

References 17 publications

Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation

Mitochondrial Impairment by MitoBloCK-6 Inhibits Liver Cancer Cell Proliferation

Identifying the Growth Factors for Improving Neointestinal Regeneration in Rats through Transcriptome Analysis Using RNA-Seq Data

Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy

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