Cell Rep. 2024 Apr 27;43(5):114163. doi: 10.1016/j.celrep.2024.114163. Online ahead of print.

ABSTRACT

Dysregulation of O-GlcNAcylation has emerged as a potential biomarker for several diseases, particularly cancer. The role of OGT (O-GlcNAc transferase) in maintaining O-GlcNAc homeostasis has been extensively studied; nevertheless, the regulation of OGA (O-GlcNAcase) in cancer remains elusive. Here, we demonstrated that the multifunctional protein RBM14 is a regulator of cellular O-GlcNAcylation. By investigating the correlation between elevated O-GlcNAcylation and increased RBM14 expression in lung cancer cells, we discovered that RBM14 promotes ubiquitin-dependent proteasomal degradation of OGA, ultimately mediating cellular O-GlcNAcylation levels. In addition, RBM14 itself is O-GlcNAcylated at serine 521, regulating its interaction with the E3 ligase TRIM33, consequently affecting OGA protein stability. Moreover, we demonstrated that mutation of serine 521 to alanine abrogated the oncogenic properties of RBM14. Collectively, our findings reveal a previously unknown mechanism for the regulation of OGA and suggest a potential therapeutic target for the treatment of cancers with dysregulated O-GlcNAcylation.

PMID:38678556 | DOI:10.1016/j.celrep.2024.114163

Sci Rep. 2024 Apr 27;14(1):9678. doi: 10.1038/s41598-024-60081-y.

ABSTRACT

Lifestyle modifications, metformin, and linagliptin reduce the incidence of type 2 diabetes (T2D) in people with prediabetes. The gut microbiota (GM) may enhance such interventions' efficacy. We determined the effect of linagliptin/metformin (LM) vs metformin (M) on GM composition and its relationship to insulin sensitivity (IS) and pancreatic β-cell function (Pβf) in patients with prediabetes. A cross-sectional study was conducted at different times: basal, six, and twelve months in 167 Mexican adults with prediabetes. These treatments increased the abundance of GM SCFA-producing bacteria M (Fusicatenibacter and Blautia) and LM (Roseburia, Bifidobacterium, and [Eubacterium] hallii group). We performed a mediation analysis with structural equation models (SEM). In conclusion, M and LM therapies improve insulin sensitivity and Pβf in prediabetics. GM is partially associated with these improvements since the SEM models suggest a weak association between specific bacterial genera and improvements in IS and Pβf.

PMID:38678119 | DOI:10.1038/s41598-024-60081-y

Cortex. 2024 Apr 8:S0010-9452(24)00089-3. doi: 10.1016/j.cortex.2024.02.018. Online ahead of print.

ABSTRACT

Trust is a key component of human relationships. Sex differences in trust behavior have been elucidated by parental investment theory and social role theory, attributing men's higher trust propensity to their increased engagement in physically and socially risky activities aimed at securing additional resources. Although sex differences in trust behavior exist and the neuropsychological signatures of trust are known, the underlying anatomical structure of sex differences is still unexplored. Our study aimed to investigate the anatomical structure of sex differences in trust behavior toward strangers (i.e., trust propensity, TP) by employing voxel-based morphometry (VBM) in a sample of healthy young adults. We collected behavioral data for TP as measured with participants in the role of trustors completing the one-shot trust game (TG) with anonymous partners as trustees. We conducted primary region of interest (ROI) and exploratory whole-brain (WB) VBM analyses of high-resolution structural images to test for the association between TP and regional gray matter volume (GMV) associated with sex differences. Confirming previous studies, our behavioral results demonstrated that men trusted more than women during the one-shot TG. Our WB analysis showed a greater GMV related to TP in men than women in the precuneus (PreC), whereas our ROI analysis in regions of the default-mode network (dorsomedial prefrontal cortex [dmPFC], PreC, superior temporal gyrus) to simulate the partner's trustworthiness, central-executive network (ventrolateral PFC) to implement a calculus-based trust strategy, and action-perception network (precentral gyrus) to performance cost-benefit calculations, as proposed by a neuropsychoeconomic model of trust. Our findings advance the neuropsychological understanding of sex differences in TP, which has implications for interpersonal partnerships, financial transactions, and societal engagements.

PMID:38677959 | DOI:10.1016/j.cortex.2024.02.018

Plant Physiol Biochem. 2024 Apr 23;210:108658. doi: 10.1016/j.plaphy.2024.108658. Online ahead of print.

ABSTRACT

In gramineae-soybean intercropping systems, shade stress caused by taller plants impacts soybean growth specifically during the reproductive stage. However, the effects of shade stress on soybean senescence remain largely unexplored. In this research, we applied artificial shade treatments with intensities of 75% (S75) and 50% (S50) to soybean plants at the onset of flowering to simulate the shade stress experienced by soybeans in the traditional and optimized maize-soybean intercropping systems, respectively. Compared to the normal light control, both shade treatments led to a rapid decline in the dry matter content of soybean vegetative organs and accelerated their abscission. Moreover, shade treatments triggered the degradation of chlorophyll and soluble proteins in leaves and increased the expression of genes associated with leaf senescence. Metabolic profiling further revealed that ethylene biosynthesis and signal transduction were induced by shade treatment. In addition, the examination of nitrogen content demonstrated that shade treatments impeded the remobilization of nitrogen in vegetative tissues, consequently reducing the seed nitrogen harvest. It's worth noting that these negative effects were less pronounced under the S50 treatment compared to the S75 treatment. Taken together, this research demonstrates that shade stress during the reproductive stage accelerates soybean senescence and impedes nitrogen remobilization, while optimizing the field layout to improve soybean growth light conditions could mitigate these challenges in the maize-soybean intercropping system.

PMID:38677188 | DOI:10.1016/j.plaphy.2024.108658

Comput Biol Med. 2024 Apr 24;175:108499. doi: 10.1016/j.compbiomed.2024.108499. Online ahead of print.

ABSTRACT

Familial hypertrophic cardiomyopathy (HCM) is a significant precursor of heart failure and sudden cardiac death, primarily caused by mutations in sarcomeric and structural proteins. Despite the extensive research on the HCM genotype, the complex and context-specific nature of many signaling and metabolic pathways linking the HCM genotype to phenotype has hindered therapeutic advancements for patients. Here, we have developed a computational model of HCM encompassing cardiomyocyte signaling and metabolic networks and their associated interactions. Utilizing a stochastic logic-based ODE approach, we linked cardiomyocyte signaling to the metabolic network through a gene regulatory network and post-translational modifications. We validated the model against published data on activities of signaling species in the HCM context and transcriptomes of two HCM mouse models (i.e., R403Q-αMyHC and R92W-TnT). Our model predicts that HCM mutation induces changes in metabolic functions such as ATP synthase deficiency and a transition from fatty acids to carbohydrate metabolism. The model indicated major shifts in glutamine-related metabolism and increased apoptosis after HCM-induced ATP synthase deficiency. We predicted that the transcription factors STAT, SRF, GATA4, TP53, and FoxO are the key regulators of cardiomyocyte hypertrophy and apoptosis in HCM in alignment with experiments. Moreover, we identified shared (e.g., activation of PGC1α by AMPK, and FHL1 by titin) and context-specific mechanisms (e.g., regulation of Ca2+ sensitivity by titin in HCM patients) that may control genotype-to-phenotype transition in HCM across different species or mutations. We also predicted potential combination drug targets for HCM (e.g., mavacamten plus ROS inhibitors) preventing or reversing HCM phenotype (i.e., hypertrophic growth, apoptosis, and metabolic remodeling) in cardiomyocytes. This study provides new insights into mechanisms linking genotype to phenotype in familial hypertrophic cardiomyopathy and offers a framework for assessing new treatments and exploring variations in HCM experimental models.

PMID:38677172 | DOI:10.1016/j.compbiomed.2024.108499

Nucleic Acids Res. 2024 Apr 27:gkae284. doi: 10.1093/nar/gkae284. Online ahead of print.

ABSTRACT

MicroRNAs (miRNAs) that share identical or near-identical sequences constitute miRNA families and are predicted to act redundantly. Yet recent evidence suggests that members of the same miRNA family with high sequence similarity might have different roles and that this functional divergence might be rooted in their precursors' sequence. Current knock-down strategies such as antisense oligonucleotides (ASOs) or miRNA sponges cannot distinguish between identical or near identical miRNAs originating from different precursors to allow exploring unique functions of these miRNAs. We here develop a novel strategy based on short 2'-OMe/LNA-modified oligonucleotides to selectively target specific precursor molecules and ablate the production of individual members of miRNA families in vitro and in vivo. Leveraging the highly conserved Xenopus miR-181a family as proof-of-concept, we demonstrate that 2'-OMe/LNA-ASOs targeting the apical region of pre-miRNAs achieve precursor-selective inhibition of mature miRNA-5p production. Furthermore, we extend the applicability of our approach to the human miR-16 family, illustrating its universality in targeting precursors generating identical miRNAs. Overall, our strategy enables efficient manipulation of miRNA expression, offering a powerful tool to dissect the functions of identical or highly similar miRNAs derived from different precursors within miRNA families.

PMID:38676942 | DOI:10.1093/nar/gkae284

STAR Protoc. 2024 Apr 26;5(2):103036. doi: 10.1016/j.xpro.2024.103036. Online ahead of print.

ABSTRACT

Neurons that originate from pre-vertebral sympathetic ganglia, the splanchnic-celiac-superior mesenteric ganglion complex (SCSMG) in mouse, have important roles in control of organs of the upper abdomen. Here, we present a protocol for the isolation of the mouse sympathetic SCSMG. We describe steps for surgical incision, ganglia isolation, ganglia fine dissection, and whole-mount SCSMG after clearing-enhanced 3D (Ce3D) clearing method and immunohistochemistry. Given the importance of mice in studies of that control, this protocol aims to assist biomedical researchers in the dissection of the mouse SCSMG.

PMID:38676927 | DOI:10.1016/j.xpro.2024.103036

Cell Rep. 2024 Apr 25;43(5):114146. doi: 10.1016/j.celrep.2024.114146. Online ahead of print.

ABSTRACT

We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term "forerunner" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two of these genes, LPAR6 and CAB39L, are preferentially downregulated in the luminal and basal subtypes of bladder cancer, respectively. Their loss of function dysregulates urothelial differentiation, sensitizing the urothelium to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced cancers, which recapitulate the luminal and basal subtypes of human bladder cancer.

PMID:38676926 | DOI:10.1016/j.celrep.2024.114146

J Exp Bot. 2024 Apr 27:erae194. doi: 10.1093/jxb/erae194. Online ahead of print.

ABSTRACT

Redox reactions are fundamental to energy conversion in living cells, and also determine and tune responses to the environment. Within this context, the tripeptide glutathione plays numerous roles. As an important antioxidant, glutathione confers redox stability on the cell and also acts an interface between signalling pathways and metabolic reactions that fuel growth and development. It also contributes to the assembly of cell components, biosynthesis of sulphur-containing metabolites, inactivation of potentially deleterious compounds, and control of hormonal signalling intensity. The multiplicity of these roles probably explains why glutathione status has been implicated in influencing plant responses to many different conditions. In particular, there is now a considerable body of evidence that glutathione is a crucial player in governing the outcome of biotic stresses. This review provides an overview of glutathione synthesis, transport, degradation, and redox turnover in plants. It examines the expression of genes associated with these processes during pathogen challenge and related conditions, and considers the diversity of mechanisms by which glutathione can influence protein function and gene expression.

PMID:38676714 | DOI:10.1093/jxb/erae194

J Exp Bot. 2024 Apr 27:erae195. doi: 10.1093/jxb/erae195. Online ahead of print.

ABSTRACT

The plant cell wall provides a strong yet flexible barrier to protect cells from the external environment. Modifications of the cell wall, either during development or under stress conditions, can induce cell wall integrity responses and ultimately lead to alterations in gene expression, hormone production, and cell wall composition. These changes in cell wall composition presumably require remodelling of the secretory pathway to facilitate synthesis and secretion of cell wall components and cell wall synthesis enzymes from the Golgi apparatus. Here, we used a combination of live-cell confocal imaging and transmission electron microscopy to examine the short-term and constitutive impact of isoxaben, which reduces cellulose biosynthesis, and Driselase, a cocktail of cell-wall-degrading fungal enzymes, on cellular processes during cell wall integrity responses. We show that both treatments altered organelle morphology and triggered rebalancing of the secretory pathway to promote secretion while reducing endocytic trafficking. The actin cytoskeleton was less dynamic following cell wall modification, and organelle movement was reduced. These results demonstrate active remodelling of the endomembrane system and actin cytoskeleton following changes to the cell wall.

PMID:38676707 | DOI:10.1093/jxb/erae195

Eur J Immunol. 2024 Apr 27:e2451155. doi: 10.1002/eji.202451155. Online ahead of print.

NO ABSTRACT

PMID:38676471 | DOI:10.1002/eji.202451155

Proteomics. 2024 Apr 27:e2300292. doi: 10.1002/pmic.202300292. Online ahead of print.

ABSTRACT

The cuticles of arthropods provide an interface between the organism and its environment. Thus, the cuticle's structure influences how the organism responds to and interacts with its surroundings. Here, we used label-free quantification proteomics to provide a proteome of the moulted cuticle of the aquatic crustacean Daphnia magna, which has long been a prominent subject of studies on ecology, evolution, and developmental biology. We detected a total of 278 high-confidence proteins. Using protein sequence domain and functional enrichment analyses, we identified chitin-binding structural proteins and chitin-modifying enzymes as the most abundant protein groups in the cuticle proteome. Structural cuticular protein families showed a similar distribution to those found in other arthropods and indicated proteins responsible for the soft and flexible structure of the Daphnia cuticle. Finally, cuticle protein genes were also clustered as tandem gene arrays in the D. magna genome. The cuticle proteome presented here will be a valuable resource to the Daphnia research community, informing genome annotations and investigations on diverse topics such as the genetic basis of interactions with predators and parasites.

PMID:38676470 | DOI:10.1002/pmic.202300292

Viruses. 2024 Apr 20;16(4):643. doi: 10.3390/v16040643.

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) infection can result in HIV-associated neurocognitive disorder (HAND), a spectrum of disorders characterized by neurological impairment and chronic inflammation. Combined antiretroviral therapy (cART) has elicited a marked reduction in the number of individuals diagnosed with HAND. However, there is continual, low-level viral transcription due to the lack of a transcription inhibitor in cART regimens, which results in the accumulation of viral products within infected cells. To alleviate stress, infected cells can release accumulated products, such as TAR RNA, in extracellular vesicles (EVs), which can contribute to pathogenesis in neighboring cells. Here, we demonstrate that cART can contribute to autophagy deregulation in infected cells and increased EV release. The impact of EVs released from HIV-1 infected myeloid cells was found to contribute to CNS pathogenesis, potentially through EV-mediated TLR3 (Toll-like receptor 3) activation, suggesting the need for therapeutics to target this mechanism. Three HIV-1 TAR-binding compounds, 103FA, 111FA, and Ral HCl, were identified that recognize TAR RNA and reduce TLR activation. These data indicate that packaging of viral products into EVs, potentially exacerbated by antiretroviral therapeutics, may induce chronic inflammation of the CNS observed in cART-treated patients, and novel therapeutic strategies may be exploited to mitigate morbidity.

PMID:38675983 | DOI:10.3390/v16040643

Viruses. 2024 Apr 8;16(4):572. doi: 10.3390/v16040572.

ABSTRACT

Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment-symptoms consistent with ME/CFS and Long COVID. This paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within the ECs of ME/CFS patients. This review offers conceptual advances by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research toward potentially unexplored avenues in understanding and treating this complex syndrome.

PMID:38675914 | DOI:10.3390/v16040572

Vaccines (Basel). 2024 Apr 15;12(4):417. doi: 10.3390/vaccines12040417.

ABSTRACT

Most available neutralizing antibodies are ineffective against highly mutated SARS-CoV-2 Omicron subvariants. Therefore, it is crucial to develop potent and broad-spectrum alternatives to effectively manage Omicron subvariants. Here, we constructed a high-diversity nanobody phage display library and identified nine nanobodies specific to the SARS-CoV-2 receptor-binding domain (RBD). Five of them exhibited cross-neutralization activity against the SARS-CoV-2 wild-type (WT) strain and the Omicron subvariants BA.1 and BA.4/5, and one nanobody demonstrated marked efficacy even against the Omicron subvariants BQ.1.1 and XBB.1. To enhance the therapeutic potential, we engineered a panel of multivalent nanobodies with increased neutralizing potency and breadth. The most potent multivalent nanobody, B13-B13-B13, cross-neutralized all tested pseudoviruses, with a geometric mean of the 50% inhibitory concentration (GM IC50) value of 20.83 ng/mL. An analysis of the mechanism underlying the enhancement of neutralization breadth by representative multivalent nanobodies demonstrated that the strategic engineering approach of combining two or three nanobodies into a multivalent molecule could improve the affinity between a single nanobody and spike, and could enhance tolerance toward escape mutations such as R346T and N460K. Our engineered multivalent nanobodies may be promising drug candidates for treating and preventing infection with Omicron subvariants and even future variants.

PMID:38675799 | DOI:10.3390/vaccines12040417

Molecules. 2024 Apr 18;29(8):1844. doi: 10.3390/molecules29081844.

ABSTRACT

In this study, a series of four surface-active compounds-N-alkyl betaine ethyl ester chlorides, CnBetC2Cl-were synthesized and characterized in aqueous solutions. As with other alkyl betaines, these amphiphiles can be practically used, for example, as co-surfactants and/or solubility enhancers acting according to hydrotropic or micellar mechanisms, depending on the alkyl chain length in the amine. We focused on the representatives of the medium alkyl chain length (C6-C12) to find the dependence between the alkyl chain length in N-alkyl betaine ethyl ester chlorides and the surface, volumetric, acoustic, and viscometric properties of their solutions. Ethyl esters, the derivatives of amino acids, were chosen to increase functionality and take advantage of possible hydrolysis in solutions at higher pH, which is also a key parameter in biodegradability. The micellization parameters were calculated based on the physicochemical characteristics. We focused our interest on the ester with a dodecyl substituent since we can compare and discuss its properties with some other C12 representatives that are available in literature. Surprisingly, its micellization characteristic is almost temperature-independent in the investigated temperature range, t = (15-45) °C. Particularly interesting are the results of dynamic light scattering (DLS), which show that the changes in physicochemical parameters of the C12 homolog around the CMC are caused by the two types of micelles of different sizes present in solutions.

PMID:38675666 | DOI:10.3390/molecules29081844

Pharmaceutics. 2024 Apr 19;16(4):556. doi: 10.3390/pharmaceutics16040556.

ABSTRACT

Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.

PMID:38675217 | DOI:10.3390/pharmaceutics16040556

Microorganisms. 2024 Apr 10;12(4):768. doi: 10.3390/microorganisms12040768.

ABSTRACT

Different bacterial species have dramatically different generation times, from 20-30 min in Escherichia coli to about two weeks in Mycobacterium leprae. The translation machinery in a cell needs to synthesize all proteins for a new cell in each generation. The three subprocesses of translation, i.e., initiation, elongation, and termination, are expected to be under stronger selection pressure to optimize in short-generation bacteria (SGB) such as Vibrio natriegens than in the long-generation Mycobacterium leprae. The initiation efficiency depends on the start codon decoded by the initiation tRNA, the optimal Shine-Dalgarno (SD) decoded by the anti-SD (aSD) sequence on small subunit rRNA, and the secondary structure that may embed the initiation signals and prevent them from being decoded. The elongation efficiency depends on the tRNA pool and codon usage. The termination efficiency in bacteria depends mainly on the nature of the stop codon and the nucleotide immediately downstream of the stop codon. By contrasting SGB with long-generation bacteria (LGB), we predict (1) SGB to have more ribosome RNA operons to produce ribosomes, and more tRNA genes for carrying amino acids to ribosomes, (2) SGB to have a higher percentage of genes using AUG as the start codon and UAA as the stop codon than LGB, (3) SGB to exhibit better codon and anticodon adaptation than LGB, and (4) SGB to have a weaker secondary structure near the translation initiation signals than LGB. These differences between SGB and LGB should be more pronounced in highly expressed genes than the rest of the genes. We present empirical evidence in support of these predictions.

PMID:38674712 | DOI:10.3390/microorganisms12040768

Microorganisms. 2024 Mar 29;12(4):695. doi: 10.3390/microorganisms12040695.

ABSTRACT

Bacteriophages (phages) are potential alternatives to chemical antimicrobials against pathogens of public health significance. Understanding the diversity and host specificity of phages is important for developing effective phage biocontrol approaches. Here, we assessed the host range, morphology, and genetic diversity of eight Salmonella enterica phages isolated from a wastewater treatment plant. The host range analysis revealed that six out of eight phages lysed more than 81% of the 43 Salmonella enterica isolates tested. The genomic sequences of all phages were determined. Whole-genome sequencing (WGS) data revealed that phage genome sizes ranged from 41 to 114 kb, with GC contents between 39.9 and 50.0%. Two of the phages SB13 and SB28 represent new species, Epseptimavirus SB13 and genera Macdonaldcampvirus, respectively, as designated by the International Committee for the Taxonomy of Viruses (ICTV) using genome-based taxonomic classification. One phage (SB18) belonged to the Myoviridae morphotype while the remaining phages belonged to the Siphoviridae morphotype. The gene content analyses showed that none of the phages possessed virulence, toxin, antibiotic resistance, type I-VI toxin-antitoxin modules, or lysogeny genes. Three (SB3, SB15, and SB18) out of the eight phages possessed tailspike proteins. Whole-genome-based phylogeny of the eight phages with their 113 homologs revealed three clusters A, B, and C and seven subclusters (A1, A2, A3, B1, B2, C1, and C2). While cluster C1 phages were predominantly isolated from animal sources, cluster B contained phages from both wastewater and animal sources. The broad host range of these phages highlights their potential use for controlling the presence of S. enterica in foods.

PMID:38674639 | DOI:10.3390/microorganisms12040695

Int J Mol Sci. 2024 Apr 21;25(8):4548. doi: 10.3390/ijms25084548.

ABSTRACT

Colorectal cancer (CRC) is the third most prevalent cancer to be diagnosed, and it has a substantial mortality rate. Despite numerous studies being conducted on CRC, it remains a significant health concern. The disease-free survival rates notably decrease as CRC progresses, emphasizing the urgency for effective diagnostic and therapeutic approaches. CRC development is caused by environmental factors, which mostly lead to the disruption of signaling pathways. Among these pathways, the Wingless/Integrated (Wnt) signaling pathway, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway, Mitogen-Activated Protein Kinase (MAPK) signaling pathway, Transforming Growth Factor-β (TGF-β) signaling pathway, and p53 signaling pathway are considered to be important. These signaling pathways are also regulated by non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They have emerged as crucial regulators of gene expression in CRC by changing their expression levels. The altered expression patterns of these ncRNAs have been implicated in CRC progression and development, suggesting their potential as diagnostic and therapeutic targets. This review provides an overview of the five key signaling pathways and regulation of ncRNAs involved in CRC pathogenesis that are studied to identify promising avenues for diagnosis and treatment strategies.

PMID:38674135 | DOI:10.3390/ijms25084548