Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins

Pecoraro, Annalisa; Pagano, Mario; Russo, Giulia; Russo, Annapina

doi:10.3390/ijms22115496

Cited by 107 publications

(73 citation statements)

References 115 publications

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“…The mitochondrial ribosome is the organelle in eukaryotic cells that synthesize 13 inner membrane proteins of the oligomeric complex required for OXPHOS [122,123]. Mitochondrial ribosome is essential for ribosomal RNA processing, modification, and binding to ribosomal proteins and cellular respiration, a process linked to cell growth and proliferation [124]. Several mitochondrial ribosomal proteins, notably the death-associated proteins 3 (DAP3) and programmed cell death protein 9 (PDCD9), have been identified as apoptosis-inducing agents in several investigations [125,126].…”

Section: Mitochondrial Ribosome and Ribosomal Proteins (Mrp)mentioning

confidence: 99%

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Bahar

Han

Kim

et al. 2022

Cancers

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Cancer chemotherapy resistance is one of the most critical obstacles in cancer therapy. One of the well-known mechanisms of chemotherapy resistance is the change in the mitochondrial death pathways which occur when cells are under stressful situations, such as chemotherapy. Mitophagy, or mitochondrial selective autophagy, is critical for cell quality control because it can efficiently break down, remove, and recycle defective or damaged mitochondria. As cancer cells use mitophagy to rapidly sweep away damaged mitochondria in order to mediate their own drug resistance, it influences the efficacy of tumor chemotherapy as well as the degree of drug resistance. Yet despite the importance of mitochondria and mitophagy in chemotherapy resistance, little is known about the precise mechanisms involved. As a consequence, identifying potential therapeutic targets by analyzing the signal pathways that govern mitophagy has become a vital research goal. In this paper, we review recent advances in mitochondrial research, mitophagy control mechanisms, and their implications for our understanding of chemotherapy resistance.

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Section: Mitochondrial Ribosome and Ribosomal Proteins (Mrp)mentioning

confidence: 99%

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Bahar

Han

Kim

et al. 2022

Cancers

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“…The protein Imp3 localizes to nucleoli and interacts with the U3 snoRNA, and is essential for the early cleavage steps in pre-rRNA processing (31). As reported in a previous study, pre-rRNA processing plays a key role in ribosome synthesis, which leads to cell growth and represents specific hallmarks of cancer cells (32). Furthermore, increasing evidence indicates the existence of a strong relationship between the aberrant rRNA synthesis and the development of cancers: on the one hand, altered rRNA processing may reduce the stability of the p53 gene, causing p53 to lose its tumor suppressor function; on the other hand, abnormal ribosomal biosynthesis causes altered translation and may result in increased translation of oncogenes and impaired translation of tumor suppressor genes (33).…”

Section: Discussionmentioning

confidence: 74%

Smoking, DNA Methylation, and Breast Cancer: A Mendelian Randomization Study

et al. 2021

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BackgroundSmoking was strongly associated with breast cancer in previous studies. Whether smoking promotes breast cancer through DNA methylation remains unknown.MethodsTwo-sample Mendelian randomization (MR) analyses were conducted to assess the causal effect of smoking-related DNA methylation on breast cancer risk. We used 436 smoking-related CpG sites extracted from 846 middle-aged women in the ARIES project as exposure data. We collected summary data of breast cancer from one of the largest meta-analyses, including 69,501 cases for ER+ breast cancer and 21,468 cases for ER− breast cancer. A total of 485 single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for smoking-related DNA methylation. We further performed an MR Steiger test to estimate the likely direction of causal estimate between DNA methylation and breast cancer. We also conducted colocalization analysis to evaluate whether smoking-related CpG sites shared a common genetic causal SNP with breast cancer in a given region.ResultsWe established four significant associations after multiple testing correction: the CpG sites of cg2583948 [OR = 0.94, 95% CI (0.91–0.97)], cg0760265 [OR = 1.07, 95% CI (1.03–1.11)], cg0420946 [OR = 0.95, 95% CI (0.93–0.98)], and cg2037583 [OR =1.09, 95% CI (1.04–1.15)] were associated with the risk of ER+ breast cancer. All the four smoking-related CpG sites had a larger variance than that in ER+ breast cancer (all p < 1.83 × 10−11) in the MR Steiger test. Further colocalization analysis showed that there was strong evidence (based on PPH4 > 0.8) supporting a common genetic causal SNP between the CpG site of cg2583948 [with IMP3 expression (PPH4 = 0.958)] and ER+ breast cancer. There were no causal associations between smoking-related DNA methylation and ER− breast cancer.ConclusionsThese findings highlight potential targets for the prevention of ER+ breast cancer. Tissue-specific epigenetic data are required to confirm these results.

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“…In this context, high mitochondrial translation may be required to support the bioenergetic needs of cancer cells. Additionally, emerging evidence suggests that the mitochondrial ribosomal proteins, beside their role in mitoribosomes assembly, also exhibit moonlight functions in the regulation of cell cycle progression and apoptosis signaling ( 141 ). Therefore, it is not surprising that altered expression of mitochondrial translational machinery components has been identified in different tumor types ( 46 , 47 , 142 ).…”

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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Ribosome Biogenesis and Cancer: Overview on Ribosomal Proteins

Cited by 107 publications

References 115 publications

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Chemotherapy Resistance: Role of Mitochondrial and Autophagic Components

Smoking, DNA Methylation, and Breast Cancer: A Mendelian Randomization Study

Targeting Mitochondrial Protein Expression as a Future Approach for Cancer Therapy

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