Biology subjects

Liu, H.

Publications and source records attributed to Liu, H..

At least 343 records · Page 19Linked to original sources

bioRxiv2024

Nuclear effects play an important role in determining codon usage-dependent human gene expression

Codon usage biases play a significant role in determining gene expression levels. Codon usage was thought to primarily influence translation-dependent processes. Here we show that codon usage optimality correlates genome-wide with nuclear mRNA and transcription levels in human cells, suggesting a nuclear role for codon usage. A genome-wide non-biased CRISPR-Cas9 screen was performed to identify factors involved in codon usage effects on gene expression. The identified factors include the CCR4-NOT complex subunit CNOT4 and many nuclear factors, including nuclear RNA exosome, PAXT complex components, and transcription factors. The CCR4-NOT complex has been shown to affect codon usage-dependent co-translational mRNA decay in yeast. Surprisingly, human CNOT4 was found to be highly enriched in nucleus and its influence on codon usage-dependent gene expression is largely caused by its impact on nuclear RNA levels due to transcriptional effect. On the other hand, nuclear exosome and PAXT complex, regulates nuclear mRNA stability through the RNA quality control pathway, leading to preferential cytoplasmic accumulation of mRNAs with optimal codon usage. Overall, our findings suggest that codon usage biases are due to selection on both translation-dependent and independent processes; different nuclear mechanisms play a key role in determining nucleotide composition-dependent gene expression levels in human cells.

genomics↗

bioRxiv2024

Force-dependent Reorganization and Mechanostability of the Izumo1:Juno Complex Involved in Human Fertilization

Izumo1:Juno-mediated adhesion between sperm and egg cells is essential for mammalian sexual reproduction. However, conventional biophysical and structural approaches have provided only limited functional insights. Using atomic force microscopy-based single- molecule force spectroscopy and all-atom steered molecular dynamic simulations, we explored the role of mechanical forces in regulating the human Izumo1:Juno complex. Our findings reveal a multi-state catch bond capable of withstanding forces up to 600 pN- mechanostability rarely observed among eukaryotic protein complexes. We further found that this mechanostability was impaired in the infertility-associated mutant, JunoH177Q. Detailed steered molecular dynamics simulations show how force-dependent reorganization of the Izumo1:Juno complex engages new binding conformations to achieve this state of high mechanostability. Overall, this study significantly enhances our understanding of the mechanical underpinnings that regulate human fertilization.

biophysics↗

bioRxiv2024

Integration of distinct cortical inputs to primary and higher order inhibitory cells of the thalamus

The neocortex controls its own sensory input in part through top-down inhibitory mechanisms. Descending corticothalamic projections drive GABAergic neurons of the thalamic reticular nucleus (TRN), which govern thalamocortical cell activity via inhibition. Neurons in sensory TRN are organized into primary and higher order (HO) subpopulations, with separate intrathalamic connections and distinct genetic and functional properties. Here, we investigated top-down neocortical control over primary and HO neurons of somatosensory TRN. Projections from layer 6 of somatosensory cortex evoked stronger and more state-dependent activity in primary than in HO TRN, driven by more robust synaptic inputs and potent T-type calcium currents. However, HO TRN received additional, physiologically distinct, inputs from motor cortex and layer 5 of S1. Thus, in a departure from the canonical focused sensory layer 6 innervation characteristic of primary TRN, HO TRN integrates broadly from multiple corticothalamic systems, with unique state-dependence, extending the range of mechanisms for top-down control.

neuroscience↗

bioRxiv2024

Bacterial sensing via Neuronal Receptor Initiates Gut Mitochondrial Surveillance for Host Adaptation

Animals exist within a microbial world and are constantly challenged by pathogen infections. Microbe-mediated protection for against infection is the survival strategy for host. However, elucidating specific microbial molecules and understanding how they interact with the hosts intracellular surveillance system for protection is difficult but highly desirable. Here, by establishing "pathogen-like-bacteria" screening system, we identified E. coli mutants, including {Delta}ymcB, that act as "pathogen-like-bacteria" to defend animals against Pseudomonas aeruginosa PA14 infection by activating UPRmt. Additionally, through genetic screening, we identified neuronal transmembrane protein, MDSS-1, that is crucial for sensing {Delta}ymcB and activating intestinal UPRmt. Moreover, we demonstrated that MDSS-1 functions as a receptor in ASE neurons, responsible for detecting {Delta}ymcB. It then communicates microbial signals through neuropeptides, GPCR, Wnt signaling and endopeptidase inhibitors to trigger intestinal UPRmt, that defends the host animals against infections. Furthermore, Constitutionally activation of MDSS-1 in ASE neurons is sufficient to trigger intestinal UPRmt in animals, resulting in protection against infection. Our study uncovers an intriguing mechanism involving intracellular mitochondrial surveillance, where neuron-intestine crosstalk originates from ASE neurons to detect bacteria and combat pathogens. This study identifies a bacteria-sensing mechanism in neurons that regulates intestinal mitochondrial surveillance pathway for host adaptation. HighlightsO_LIEstablishment of "pathogen-like-bacteria" screening system in C. elegans C_LIO_LI{Delta}ymcB promotes animal defend against infections via triggering UPRmt C_LIO_LINeuronal MDSS-1, a single transmembrane protein, detects "pathogen-like-bacteria" C_LIO_LIActivated-MDSS-1 induces distant UPRmt via inter-tissue communication factors C_LI

physiology↗

bioRxiv2024

Semantic Inhibition and Reactivation for Transcending from Semantic Understanding to Aesthetic Appreciation: fNIRS Evidence from Aesthetic Reading

BackgroundAesthetic education is pivotal in shaping a comprehensive and harmonious humanity. However, the transition from semantic comprehension to aesthetic appreciation remains poorly understood. This study, informed by transactional theory, sought to elucidate the cognitive mechanisms of aesthetic reading by examining its neural dynamics through functional Near-Infrared Spectroscopy. MethodsParticipants were tasked with reading Tang poetry aesthetically, with fNIRS monitoring brain activity in frontal and temporal regions. ResultsCompared to an efferent reading task, the aesthetic reading task revealed a distinct three-stage neural dynamic pattern. Initially, aesthetic reading showed similar HbO activation in all regions, likely indicating the semantic processing phase. This was followed by a divergence, with a decrease in HbO over the left primary somatosensory cortex and the left superior, inferior, and middle temporal gyri, suggesting inhibition of semantic processing. Finally, a resurgence of activity in these areas was observed, along with an increase in HbO over the left dorsolateral prefrontal cortex, which could be associated with memory, imagination, and empathy. This reactivation correlated with participants self-reported aesthetic appreciation scores. ContributionThe findings reveal the temporal and spatial dynamics of brain activity during aesthetic reading, enhancing our comprehension of underlying cognitive processes.

neuroscience↗

bioRxiv2024

Protein Kinases in Phagocytosis: Promising Genetic Biomarkers for Cancer

Cancer is a complex disease characterized by genetic and molecular diversity, often involving dysregulation of critical cellular pathways. Recent advances in pan-cancer research have highlighted the importance of shared oncogenic mechanisms across different cancer types, providing new avenues for therapeutic exploration. Protein kinases, particularly those involved in phagocytosis, play pivotal roles in cellular homeostasis and immune response. This study systematically examines the genetic alterations and expression profiles of protein kinases associated with phagocytosis across various cancer types, using data from The Cancer Genome Atlas (TCGA) and other publicly available resources. We analyzed single nucleotide variations (SNVs), copy number variations (CNVs), methylation patterns, and mRNA expression to identify recurring alterations and their associations with survival outcomes. Our findings reveal that MET and MERTK are the most frequently mutated genes, with missense mutations dominating across cancers. CNV analysis shows significant correlations with survival in cancers like UCEC, KIRP, and KIRC, while methylation analysis indicates cancer-specific regulatory patterns affecting gene expression. Differential expression analysis highlights distinct cancer-type-specific expression profiles, with genes like MET and BTK displaying significant variation. Crosstalk pathway analysis further reveals the involvement of these kinases in key cancer-related pathways, such as epithelial-mesenchymal transition (EMT) and apoptosis. Drug sensitivity analysis identifies potential therapeutic targets, with gene expression correlating significantly with cancer cell line responsiveness to specific compounds. These findings underscore the importance of the phagocytotic kinome in cancer biology and suggest potential therapeutic strategies targeting protein kinases to enhance immune response and improve treatment outcomes.

genetics↗

bioRxiv2024

CRISPR tiling deletion screens reveal functional enhancers of neuropsychiatric risk genes and allelic compensation effects (ACE) on transcription

Precise transcriptional regulation is critical for cellular function and development, yet the mechanism of this process remains poorly understood for many genes. To gain a deeper understanding of the regulation of neuropsychiatric disease risk genes, we identified a total of 39 functional enhancers for four dosage-sensitive genes, APP, FMR1, MECP2, and SIN3A, using CRISPR tiling deletion screening in human induced pluripotent stem cell (iPSC)-induced excitatory neurons. We found that enhancer annotation provides potential pathological insights into disease-associated copy number variants. More importantly, we discovered that allelic enhancer deletions at SIN3A could be compensated by increased transcriptional activities from the other intact allele. Such allelic compensation effects (ACE) on transcription is stably maintained during differentiation and, once established, cannot be reversed by ectopic SIN3A expression. Further, ACE at SIN3A occurs through dosage sensing by the promoter. Together, our findings unravel a regulatory compensation mechanism that ensures stable and precise transcriptional output for SIN3A, and potentially other dosage-sensitive genes.

genetics↗

bioRxiv2024

Evidence of opportunistic blood feeding in the parasitic nematode Heligmosomoides bakeri

Haem, which binds iron and oxygen, is essential for parasitic nematode growth. Nematodes lack endogenous haem synthesis pathways and acquire haem from their environment or intracellular symbionts. Genes involved in haem degradation and detoxification have been identified in parasitic nematodes who are either specialised blood feeders (haematophages) or reside in the blood stream. Targeting these genes, so limiting parasite growth and promoting parasite death, provides a new therapeutic avenue against blood feeding parasitic nematodes. Heligmosomoides bakeri, a model intestinal parasitic nematode, has not been considered a blood feeder. Adults live in the intestinal lumen and graze on host tissue. However, the earlier larval stages enter the intestinal tissue, where they grow and moult multiple times, an oxygen demanding process. We have shown that, in vivo, likely through nematode-induced damage, many tissue-dwelling H. bakeri are in close vicinity of red blood cells. During this time, infection induces host anemia. Further, tissue-dwelling H. bakeri that have fed on blood have an increased expression of collagen genes compared to those parasites that had not fed on blood. In vitro, this translates to a growth advantage. Our findings suggest blood feeding is more widespread among nematodes than currently described. We argue that biochemical adaptations previously considered to be limited to blood-feeders are found in other nematodes. Moreover, H. bakeri can serve as a model for studying blood-feeding mechanisms and developing anthelminthic strategies to them.

zoology↗

bioRxiv2024

Environmental polysulfides promote protein disulfide bond formation of microorganisms growing under anaerobic condition

Polysulfides are rich in anaerobic and microbial metabolism active environments. Anaerobic survival of microorganisms requires the formation of protein disulfide bond (DSB). The relation between environmental polysulfides and anaerobic DSB formation has not been studied so far. Herein, we discovered that environmental polysulfides can efficiently mediate protein DSB formation of microorganisms under anaerobic condition. We used polysulfides to treat proteins including roGFP2, Trx1, and DsbA under anaerobic condition and found that all three proteins formed intramolecular DSB in vitro. The growth of E. coli {Delta}dsbB was reduced and the amount of its intracellular protein DSB was decreased under anaerobic condition. However, treating the mutant strain with polysulfides recovered the growth and reversed DSB decrease. Treating E. coli {Delta}dsbA with polysulfides promoted DSB formation of its periplasmic roGFP2 and recovered its growth under anaerobic condition. In addition, treating Schizosaccharomyces pombe with polysulfides led to increase of the intracellular protein DSB content. Thus, our study reveals that environmental polysulfides can promote DSB formation independent of the enzymatic DSB mediating system and oxygen. In this aspect, environmental polysulfides are beneficial for the survival of microorganisms in anaerobic habitats. IMPORTANCEHow polysulfides benefit adaption of microorganisms to anaerobic environments are unclear. Our study reveals that environmental polysulfides efficiently facilitate protein DSB formation under anaerobic condition. Polysulfides contain zero valent sulfur atoms (S0), which can be transferred to the thiol group of cysteine residue. This S0 atom gets two electrons from two cysteine residues and becomes reduced H2S, leaving two cysteine residues in disulfide bond form. Anaerobic growth of microorganisms was benefited from the formation of DSB. This finding paves the way for a deeper understanding of the intricate relationship between polysulfides and microorganisms in environmental contexts.

molecular biology↗

bioRxiv2024

Multi-omics analysis reveals the mechanism of BnC07MYB3a is involved in seed coat color in Brassica napus L.

In rapeseed (Brassica napus), yellow-seeded varieties accumulate less flavonoid pigments (anthocyanins/proanthocyanidins) in their seed coats compared with black-seeded varieties. The yellow-seeded trait is associated with greatly improved seed oil yield, quality, and commercial value. Many R2R3 MYB activators have been characterized in rapeseed, but how MYB-type repressors affect pigment biosynthesis is not yet fully understood. In this study, we performed transcriptome sequencing and metabolomic analysis of B. napus varieties with extreme differences in seed coat color, combined with weighted gene co-expression network analysis. This analysis identified an R2R3-MYB-type transcription factor, BnC07MYB3a (BnaC07G0178800ZS), as a candidate regulator of the yellow-seeded trait in B. napus. Overexpressing BnC07MYB3a in Arabidopsis thaliana and B. napus downregulated the expression of flavonoid biosynthetic genes, resulting in significantly lower anthocyanin and proanthocyanidin accumulation than in the wild-type and a lighter seed coat color in transgenic plants. BnC07MYB3a directly binds to the promoter of the TRANSPARENT TESTA (TT) gene BnTT6 and represses its expression. BnC07MYB3a also physically interacts with BnA06bHLH92a and the WD40 transcription factor TRANSPARENT TESTA GLABRA1 (BnTTG1), suggesting that they might form a previously unidentified MYB-bHLH-WD40 transcription factor complex. Our results reveal the molecular mechanism and regulatory network of BnC07MYB3a in determining seed coat color in B. napus and provide a genetic resource for breeding yellow-seeded cultivars of B. napus.

molecular biology↗

bioRxiv2024

CPK3-mediated cytosolic-nuclear translocation of bHLH107 recruits HY5 to regulate the Cu2+-triggered upregulation of ACS8

Copper serves as a micronutrient for plant growth and development and has been a key component of copper-based antimicrobial compounds (CBACs) for protection against plant diseases for more than 130 years. We previously revealed that nanomolar- to-micromolar concentrations of Cu2+ elicit plant immune responses by activating the expression of the ethylene synthesis rate-limiting enzyme ACS8, which is dependent on the promoter copper response element (CuRE) cis-element. Here, we genetically confirmed that Cu2+-induced resistance to Pseudomonas syringae pv. tomato (Pst) DC3000 is dependent on the CuRE in ACS8. Upon screening for CuRE-binding transcription factors, bHLH107, which is required for Cu2+-triggered activation of ACS8 expression and resistance to Pst DC3000, was identified via DNA-pull-down and mass spectrometry (MS) assays. Calcium-dependent protein kinase 3 (CPK3) interacts with and phosphorylates bHLH107 at Ser62 and Ser72 to mediate bHLH07 translocation from the cytoplasm into the nucleus, where it interacts with Arabidopsis ELONGATED HYPOCOTYL5 (HY5). HY5 directly binds to the G-box and acts as a coactivator to promote bHLH107 binding to the CuRE cis-element and to increase transcription of ACS8 upon Cu2+ treatment. Overall, we revealed a CPK3-bHLH107-HY5 module that regulates the Cu2+-responsive regulatory network upstream of ACS8 that is involved in the cytosolic-nuclear translocation of bHLH107.

plant biology↗

bioRxiv2024

Radical Protein Footprinting in Mammalian Whole Blood

Hydroxyl Radical Protein Footprinting (HRPF) is a powerful tool to probe protein higher-order structure, as well as protein-protein and protein-carbohydrate interactions. It is mostly performed in vitro, but recent advances have extended its use to live cells, nematodes, and 3D cultures. However, application in living mammalian tissues has not been accomplished. Here, we present the first successful use of radical protein footprinting (RPF) in mammalian whole blood from wild-type (WT) and type 2 diabetes mellitus (T2DM) BKS. Cg Dock7m +/+ Leprdb/J mice. Using persulfate photoactivated with the FOX Photolysis System, we achieved effective protein labeling without significant disruption to blood cell morphology. An optimized quenching protocol eliminated background labeling. We report oxidative modifications in 11 selected proteins, revealing disease-associated conformational changes in multiple proteins. These findings demonstrate the feasibility of RPF in mammalian blood and open new opportunities for structural proteomics in preclinical models and clinical samples.

biochemistry↗

bioRxiv2024

Expanding the CRISPR toolbox by engineering Cas12a orthologs of metagenomic discovery

Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility in genome editing and molecular diagnostic applications. However, the widespread adoption of CRISPR-Cas12a nucleases and their variants has been hindered by the requirement for a specific protospacer adjacent motif (PAM), relatively low CRISPR RNA (crRNA) activity and the inability to multiplex nucleic acid detection alone. To overcome these limitations, we employed a comprehensive framework combined with AlphaFold2 to de novo mine 1,261 previously unexploited Cas12a orthologs from the global microbiome. Following experimental analysis, we identified the most promising 21 Cas12a nuclease orthologs and designated them "Genie scissor 12" (Gs12). Our analysis uncovered two exceptional variants among these newly identified orthologs: Gs12-10, a first natural PAM-less Cas12a ortholog, which can recognize 52 distinct PAM types, representing a significant 1.8-fold expansion in recognition range compared to the relative LbCas12a PAM; and Gs12-7MAX, an engineered variant of Gs12-7 that exhibited 1.27-fold higher editing efficiency than enAsCas12a-HF. Furthermore, we harnessed Gs12-1, Gs12-4, Gs12-9, and Gs12-18, along with their corresponding engineered crRNAs, to develop a powerful four-channel multiplexed CRISPR-based nucleic acid detection system. The discovery of diverse functions in Cas12a offers a deeper understanding of the CRISPR/Cas12a family. Also, it holds great promise for expanding its applications and uncovering the untapped potential of other CRISPR/Cas systems. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/615316v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@bee75forg.highwire.dtl.DTLVardef@1480f61org.highwire.dtl.DTLVardef@1e9cbc9org.highwire.dtl.DTLVardef@4211b2_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2024

Lysosomal LRRC8 complex regulates lysosomal pH, morphology and systemic glucose metabolism

The lysosome integrates anabolic signalling and nutrient-sensing to regulate intracellular growth pathways. The leucine-rich repeat containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signalling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show LRRC8A regulates leucine-stimulated mTOR, lysosome size, number, pH, and expression of lysosomal proteins LAMP2, P62, LC3B, suggesting impaired autophagic flux. Mutating a LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signalling and altered lysosomal morphology and pH observed in LRRC8A KO cells. In vivo, LRRC8A-L706A;L707A KI mice exhibit increased adiposity, impaired glucose tolerance and insulin resistance characterized by reduced skeletal muscle glucose-uptake, and impaired incorporation of glucose into glycogen. These data reveal a lysosomal LRRC8 mediated metabolic signalling function that regulates lysosomal activity, systemic glucose homeostasis and insulin-sensitivity.

cell biology↗

bioRxiv2024

High-dimensional Ageome Representations of Biological Aging across Functional Modules

The aging process involves numerous molecular changes that lead to functional decline and increased disease and mortality risk. While epigenetic aging clocks have shown accuracy in predicting biological age, they typically provide single estimates for the samples and lack mechanistic insights. In this study, we challenge the paradigm that aging can be sufficiently described with a single biological age estimate. We describe Ageome, a computational framework for measuring the epigenetic age of thousands of molecular pathways simultaneously in mice and humans. Ageome is based on the premise that an organisms overall biological age can be approximated by the collective ages of its functional modules, which may age at different rates and have different biological ages. We show that, unlike conventional clocks, Ageome provides a high-dimensional representation of biological aging across cellular functions, enabling comprehensive assessment of aging dynamics within an individual, in a population, and across species. Application of Ageome to longevity intervention models revealed distinct patterns of pathway-specific age deceleration. Notably, cell reprogramming, while rejuvenating cells, also accelerated aging of some functional modules. When applied to human cohorts, Ageome demonstrated heterogeneity in predictive power for mortality risk, and some modules showed better performance in predicting the onset of age-related diseases, especially cancer, compared to existing clocks. Together, the Ageome framework offers a comprehensive and interpretable approach for assessing aging, providing insights into mechanisms and targets for intervention.

systems biology↗

bioRxiv2024

Novel regulator Fpr2 controls immune homeostasis via CCL4-dependent neutrophils

Polymorphonuclear leukocytes (PMNs) in Fpr2-deficient mice have significantly impaired bactericidal activity, yet the precise mechanism remains elusive. Our research unveiled the cellular heterogeneity of peripheral blood PMNs through single-cell RNA-sequencing (scRNA-seq) and identified two new neutrophil clusters related to bacterial infection, including a sterilization cluster named Neu_CSTA and a regulation cluster named Neu_CCL4. The lack of Fpr2 leads to an immune regulation imbalance of Neu_CCL4 on other clusters in uninfected conditions, resulting in persistent instability of PMNs in peripheral blood, elevated inflammatory factors, and increased NOX2 expression. Furthermore, our findings corroborate that the regulatory function of Neu_CCL4 on PMNs immune balance is closely tied to its high expression of the anti-inflammatory ligand Anxa1. Regulon analysis inferred by scRNA-seq and ChIP-seq data suggested that a specific transcription factor Elf4, could modulate the expression of Anxa1, thereby facilitating its regulatory impact on other clusters. In the infection state, there was a noted increase in intercellular interactions across different clusters, leading to a general improvement in the bactericidal activity of PMNs. In summary, our research revealed distinct functional cellular sub-populations of PMNs, discovered the potential regulatory mechanisms, and elucidated the essential roles of Fpr2 in their ability to resist infection.

immunology↗

bioRxiv2024

Potential Cancer Biomarkers: Mitotic Intra-S DNA Damage Checkpoint Genes

BACKGROUNDThe mitotic intra-S DNA damage checkpoint signaling gene set is potentially involved in cancers where the genes play an important role. 17 total genes are involved in this gene set: ATF2, CHEK2, EME1, EME2, FANCD2, HUS1, HUS1B, MDC1, MRE11, MSH2, MUS81, NEK11, RAD17, RAD9A, RAD9B, TIPIN, XPC. The aim of this study is to complete a pan-cancer profile of each gene in the mitotic intra-S DNA damage checkpoint signaling gene set in order to determine potential diagnostic and prognostic purposes, while also determining how they could be used in a clinical setting as therapeutic targets to help patients. METHODSMultiomic data was acquired for the 17 genes; over 9000 samples of 33 types of cancer were analyzed to create pan-cancer profiles of CNV, mRNA expression, and pathway analysis. RESULTSThe CNVs of some of these genes are associated with the survival of MESO, PCPG, BLCA, SKCM, LUAD, HNSC, LUSC, OV, and BRCA could be affected by the mRNA expression of the genes which can involve regulation of copy number. CONCLUSIONWith sufficient investigation, the genes involved in mitotic intra-S DNA damage checkpoint signaling may contribute to the development of cancer and may be used as biomarkers for cancer prognosis and diagnosis. To prove their clinical use for diagnosis and prognosis, however, and to create workable applications in clinical settings, further work is required. However, these pan-cancer profiles provide a more comprehensive knowledge of the mitotic intra-S DNA damage checkpoint signaling gene set in cancer as well as valuable information for future reference.

bioinformatics↗

bioRxiv2024

Pan-Cancer Genetic Analysis of Mitochondrial DNA Repair Gene Set

BackgroundThe mitochondrial DNA repair has gained attention for its potential impact on pan-cancer genetic analysis. This study investigates the clinical relevance of mitochondrial DNA repair genes: PARP1, DNA 2, PRIMPOL, TP53, MGME1. MethodsUsing multi-omics profiling data and Gene Set Cancer Analysis (GSCA) with normalized SEM mRNA expression, this research analyzes differential expression, gene mutation, and drug correlation. ResultsTP53 was the most commonly mutated mitochondrial-related gene in cancer, with UCS and OV having the highest mutation rates. CPG mutations linked to lowest survival rates. Breast cancer, with various subtypes, was potentially influenced by mitochondrial DNA repair genes. ACC was shown to be high in gene survival analysis. BRCA, USC, LUCS, COAD, and OV showed CNV levels impacting survival. A negative gene expression-methylation correlation was observed and was weakest in KIRC. Mitochondrial DNA repair genes were linked to Cell cycle_A activation. A weak correlation was found between immune infiltration and mitochondrial genes. Few drug compounds were shown to be affected by mitochondrial-related genes. ConclusionUnderstanding mitochondrial-related genes could redefine cancer diagnosis, and prognosis, and serve as therapeutic biomarkers, potentially altering cancer cell behavior and treatment outcomes.

bioinformatics↗