Cancer Development Research Articles

A potential association between recent increased incidence of breast and uterine body cancers in Japanese women and changes in dietary saturated fat and folate intake: A meta-analysis

Recent increases in breast and uterine body cancers among Japanese women suggest the involvement of some modifiable factors in cancer development, including drinking and smoking habits, which are generally associated with Westernized lifestyles. Using national data on annual cancer incidence, this study examines the associations between recent changes in cancer incident rates and dietary habits. Data on age-specific incidence and mortality rates of breast, uterine body, colon, and lung cancers from 2004 to 2019, as well as annual changes in the intake of animal protein, plant protein, saturated fatty acids, and folate from 2001 to 2019 among Japanese women, were obtained from e-Stat, a portal site of Japanese Government Statistics. The analysis indicates that the incidence rates of breast and uterine body cancers among Japanese women increased from 2004 to 2019, displaying distinct distribution patterns with two peaks for breast cancer and one peak for uterine body cancer. The rising incidence rates of both cancers were positively correlated with annual changes in animal protein and saturated fat intake and inversely correlated with changes in plant protein and folate intake. Health-care professionals should be aware of the notable and characteristic increase in breast and uterine body cancer incidence among Japanese women and emphasize the importance of lifestyle modifications to counteract Westernized dietary habits.

Mapping alternative splicing events in colorectal cancer

Although aberrant splicing events of genes are closely related to the development and progression of colorectal cancer (CRC), the mapping of abnormal splicing events, especially alternative splicing (AS) event types and the underlying effects, remain investigational. In the present study, we analyzed a public RNA-seq database (GSE138202) and identified 14,314 significant AS events in CRC patients compared to healthy individuals. Most of the key genes such as oncogenes involved in the development of CRC have different AS event types. Moreover, the results demonstrate that certain AS events may play a significant role in the functioning of key genes involved in splicing factors and microRNAs. Furthermore, we observed that the oncogene CDK4 in CRC tends to undergo exon 2 skipping AS events, resulting in a stronger tendency for protein expression to form complexes with CCND1, thereby inhibiting the cell cycle and weakening cell proliferation, while enhancing cell migration capability. These findings not only provide new insights into the mechanism of AS in regulating CRC, but also offers a theoretical basis for targeted splicing therapy in CRC.

Microproteins/micropeptides dysregulation contributes to cancer progression and development: A mechanistic review.

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.

Autotaxin-Lysophosphatidate Axis: Promoter of Cancer Development and Possible Therapeutic Implications.

Autotaxin (ATX) is a member of the ectonucleotide pyrophosphate/phosphodiesterase (ENPP) family; it is encoded by the ENPP2 gene. ATX is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is responsible for the transduction of various signal pathways through the interaction with at least six G protein-coupled receptors, LPA Receptors 1 to 6 (LPAR1-6). The ATX-LPA axis is involved in various physiological and pathological processes, such as angiogenesis, embryonic development, inflammation, fibrosis, and obesity. However, significant research also reported its connection to carcinogenesis, immune escape, metastasis, tumor microenvironment, cancer stem cells, and therapeutic resistance. Moreover, several studies suggested ATX and LPA as relevant biomarkers and/or therapeutic targets. In this review of the literature, we aimed to deepen knowledge about the role of the ATX-LPA axis as a promoter of cancer development, progression and invasion, and therapeutic resistance. Finally, we explored its potential application as a prognostic/predictive biomarker and therapeutic target for tumor treatment.

Cancer Diagnosis by Gene-Environment Interactions via Combination of SMOTE-Tomek and Overlapped Group Screening Approaches with Application to Imbalanced TCGA Clinical and Genomic Data

The complexity of cancer development involves intricate interactions among multiple biomarkers, such as gene-environment interactions. Utilizing microarray gene expression profile data for cancer classification is anticipated to be effective, thus drawing considerable interest in the fields of bioinformatics and computational biology. Due to the characteristics of genomic data, problems of high-dimensional interactions and noise interference do exist during the analysis process. When building cancer diagnosis models, we often face the dilemma of model adaptation errors due to an imbalance of data types. To mitigate the issues, we apply the SMOTE-Tomek procedure to rectify the imbalance problem. Following this, we utilize the overlapping group screening method alongside a binary logistic regression model to integrate gene pathway information, facilitating the identification of significant biomarkers associated with clinically imbalanced cancer or normal outcomes. Simulation studies across different imbalanced rates and gene structures validate our proposed method’s effectiveness, surpassing common machine learning techniques in terms of classification prediction accuracy. We also demonstrate that prediction performance improves with SMOTE-Tomek treatment compared to no imbalance treatment and SMOTE treatment across various imbalance rates. In the real-world application, we integrate clinical and gene expression data with prior pathway information. We employ SMOTE-Tomek and our proposed methods to identify critical biomarkers and gene-environment interactions linked to the imbalanced binary outcomes (cancer or normal) in patients from the Cancer Genome Atlas datasets of lung adenocarcinoma and breast invasive carcinoma. Our proposed method consistently achieves satisfactory classification accuracy. Additionally, we have identified biomarkers indicative of gene-environment interactions relevant to cancer and have provided corresponding estimates of odds ratios. Moreover, in high-dimensional imbalanced data, for achieving good prediction results, we recommend considering the order of balancing processing and feature screening.

Plasma-Derived Extracellular Vesicles and Non-Extracellular Vesicle Components from APCMin/+ Mice Promote Pro-Tumorigenic Activities and Activate Human Colonic Fibroblasts via the NF-κB Signaling Pathway.

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Current studies have demonstrated that tumor-derived extracellular vesicles (EVs) from different cancer cell types modulate the fibroblast microenvironment to contribute to cancer development and progression. Here, we isolated and characterized circulating large EVs (LEVs), small EVs (SEVs) and non-EV entities released in the plasma from wild-type (WT) mice and the APCMin/+ CRC mice model. Our results showed that human colon fibroblasts exposed from APC-EVs, but not from WT-EVs, exhibited the phenotypes of cancer-associated fibroblasts (CAFs) through EV-mediated NF-κB pathway activation. Cytokine array analysis on secreted proteins revealed elevated levels of inflammatory cytokine implicated in cancer growth and metastasis. Finally, non-activated cells co-cultured with supernatant from fibroblasts treated with APC-EVs showed increased mRNA expressions of CAFs markers, the ECM, inflammatory cytokines, as well as the expression of genes controlled by NF-κB. Altogether, our work suggests that EVs and non-EV components from APCMin/+ mice are endowed with pro-tumorigenic activities and promoted inflammation and a CAF-like state by triggering NF-κB signaling in fibroblasts to support CRC growth and progression. These findings provide insight into the interaction between plasma-derived EVs and human cells and can be used to design new CRC diagnosis and prognosis tools.

CD147 TagSNP is associated with the vulnerability to lung cancer in the Chinese population: a case–control study

BackgroundLung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population.MethodsA hospital-based case–control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses.ResultsBaseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype.ConclusionsCD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

Perinatal Famine Exposure and Young-Onset Cancer-Lessons from China Health and Nutrition Survey.

Background/Objectives: Perinatal exposure to malnutrition has been hypothesised to influence the development of young-onset cancer (≤50 years of age). This study aimed to determine if perinatal malnutrition in individuals exposed to the Great Famine of China increased their risk of developing young-onset cancer compared to other individuals born prior to the famine. Subjects/Methods: This cross-sectional study involved 7272 participants from the China Health and Nutrition Survey who were classified into four groups based on birth year: participants born between 1953 and 1955 (before the famine) were designated as the pre-famine group (unexposed); the remainder formed perinatal exposure groups comprised of those exposed during the famine (1959-1961), those exposed in the early post-famine period (1962-1964), and those exposed in the late post-famine period (1965-1967). Multivariable adjusted log-binomial regression models were used to calculate the RR and 95% CI of young-onset cancer (including genitourinary cancer) across four groups. Results: Perinatal exposure to early post-famine (RR 2.08; 95%CI 1.04, 4.34; p = 0.043) and the female sex (RR 15.6, 95%CI 4.54, 60.3; p < 0.001) were noted to have a significantly increased risk of young-onset cancer. In addition, the early (RR 13.8; 95%CI 2.68, 253; p = 0.012) and late post-famine (RR 12.3; 95%CI 2.16, 231; p = 0.020) cohorts demonstrated a significantly increased risk of young-onset genitourinary cancer. The latter was accompanied by an increased risk of hypertension (RR 3.30; 95%CI 1.28, 7.87; p = 0.009). Conclusions: Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. These findings highlight the potential long-term impact of perinatal malnutrition on young-onset carcinogenesis.

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling.

Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. To investigate the role of MOB3B in colorectal cancer (CRC). This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results. MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts. Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

RET Inhibitors in RET Fusion-Positive Lung Cancers: Past, Present, and Future.

While activating RET fusions are identified in various cancers, lung cancer represents the most common RET fusion-positive tumor. The clinical drug development of RET inhibitors in RET fusion-positive lung cancers naturally began after RET fusions were first identified in patient tumor samples in 2011, and thereafter paralleled drug development in RET fusion-positive thyroid cancers. Multikinase inhibitors were initially tested with limited efficacy and substantial toxicity. RET inhibitors were then designed with improved selectivity, central nervous system penetrance, and activity against RET fusions and most RET mutations, including resistance mutations. Owing their success to these rationally designed features, the first-generation selective RET tyrosine kinase inhibitors (TKIs) had higher response rates, more durable disease control, and an improved safety profile compared to the multikinase inhibitors. This led to lung and thyroid cancer, and later tumor-agnostic regulatory approvals. While next-generation RET TKIs were designed to abrogate uncommon on-target (e.g., solvent front mutation) resistance to selpercatinib and pralsetinib, many of these drugs lacked the selectivity of the first-generation TKIs, raising the question of what the future holds for drug development in RET-dependent cancers.

Effects of diets on risks of cancer and the mediating role of metabolites

Research on the association between dietary adherence and cancer risk is limited, particularly concerning overall cancer risk and its underlying mechanisms. Using the UK Biobank data, we prospectively investigate the associations between adherence to a Mediterranean diet (MedDiet) or a Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay diet (MINDDiet) and the risk of overall and 22 specific cancers, as well as the mediating effects of metabolites. Here we show significant negative associations of MedDiet and MINDDiet adherence with overall cancer risk. These associations remain robust across 14 and 13 specific cancers, respectively. Then, a sequential analysis, incorporating Cox regression, elastic net and gradient boost models, identify 10 metabolites associated with overall cancer risk. Mediation results indicate that these metabolites play a crucial role in the association between adherence to a MedDiet or a MINDDiet and cancer risk, independently and cumulatively. These findings deepen our understanding of the intricate connections between diet, metabolites, and cancer development.

Assessing the impact of MSH3 and MSH6 polymorphisms on lung cancer risk in North Indian patients undergoing platinum chemotherapy through molecular dynamics simulation

The present study investigated the relationship between MSH3 and MSH6 genes in lung cancer patients. Genotyping of lung cancer patients and healthy controls was performed. Odds ratio values were calculated and survival analysis performed. Patients with mutant genotype (TT) for MSH6 polymorphism have 1.5-fold risk for the development of lung cancer (p = 0.03). For non-smokers, the mutant-type genotype had a threefold increased risk of lung cancer (p = 0.01). Patients administered with docetaxel and carbo/cisplatin and carrying GT genotype for MSH6 polymorphism, patients reported a decrease in median survival time (4.9 vs 9.13 months). MSH3 and MSH6 polymorphisms are involved in modulating the risk towards lung cancer. MSH6 polymorphism is associated with high mortality rate for patients undergoing cisplatin and docetaxel chemotherapy.

Breast cancer, viruses, and human leukocyte antigen (HLA)

Several viruses have been implicated in breast cancer, including human herpes virus 4 (HHV4), human herpes virus 5 (HHV5), human papilloma virus (HPV), human JC polyoma virus (JCV), human endogenous retrovirus group K (HERVK), bovine leukemia virus (BLV) and mouse mammary tumor virus (MMTV). Human leukocyte antigen (HLA) is involved in virus elimination and has been shown to influence breast cancer protection/susceptibility. Here we investigated the hypothesis that the contribution of a virus to development of breast cancer would depend on the presence of the virus, which, in turn, would be inversely related to the success of its elimination. For that purpose, we estimated in silico predicted binding affinities (PBA) of proteins of the 7 viruses above to 127 common HLA alleles (69 Class I [HLA-I] and 58 Class II HLA-II]) and investigated the association of these binding affinities to the breast cancer—HLA (BC-HLA) immunogenetic profile of the same alleles. Using hierarchical tree clustering, we found that, for HLA-I, viruses BLV, JCV and MMTV were grouped with the BC-HLA, whereas, for HLA-II, viruses BLV, HERVK, HPV, JCV, and MMTV were grouped with BC-HLA. Finally, for both HLA classes, the average PBAs of the viruses grouped with the BC-HLA profile were significantly lower than those of the other, non BC-HLA associated viruses. Assuming that low PBAs are likely associated with slower viral elimination, these findings support the hypothesis that a defective/slower elimination and, hence, longer persistence and inefficient/delayed production of antibodies against them underlies the observed association of the low-PBA group with breast cancer.

Older Adults with Cancer and Common Comorbidities-Challenges and Opportunities in Improving Their Cancer Treatment Outcomes.

The older American population is rapidly increasing, and millions of older adults will be cancer survivors with comorbidities. This population faces specific challenges regarding treatment and has unique clinical needs. Recognizing this need, the National Cancer Institute (NCI), in collaboration with the National Institute on Aging (NIA), hosted a webinar series, entitled "Cancer, Aging, and Comorbidities." This commentary provides a reflection of five thematic areas covered by the webinar series, which was focused on improving cancer treatment for older adults with cancer and comorbidities: i) the impact of comorbidities on treatment tolerability and patient outcomes; ii) the impact of comorbidities on cancer clinical trial design; iii) the development of wearable devices in measuring comorbidities in cancer treatment; iv) the effects of nutrition and the microbiome on cancer therapy and; v) the role of senescence and senotherapy in age-related diseases. While advances have been made in these areas, many gaps and challenges exist and are discussed in this commentary. To improve cancer survivorship in older populations with comorbidities, aging and comorbidities must be jointly considered and incorporated across the spectrum of cancer research. This includes more basic research of the mechanisms linking comorbidities and cancer development and treatment response, building critical resources and infrastructure (eg, preclinical models and patient samples), conducting clinical trials focused on the older population, integrating geriatric assessment into cancer treatment, and incorporating novel technologies, such as wearable devices into clinical trials and cancer care.

Robust Detection of Gene Amplification in Formalin-Fixed Paraffin-Embedded Samples by Fluorescence in situ Hybridization.

Focal gene amplification, such as extrachromosomal DNA (ecDNA), plays an important role in cancer development and therapy resistance. While sequencing-based methodologies enable an unbiased identification of ecDNA, cytogenetic-based techniques, such as fluorescence in situ hybridization (FISH), remain time and cost-effective for identifying ecDNA in clinical specimens. The application of FISH in formalin-fixed paraffin-embedded (FFPE) tissue samples offers a unique avenue for detecting amplified genes, particularly when viable specimens are not available for karyotype examination. However, there is a lack of consensus procedures for this technique. This protocol provides comprehensive, fully optimized, step-by-step instructions for conducting FISH to detect gene amplification, including ecDNA, in FFPE tissue samples which present unique challenges that this protocol aims to overcome and standardize. By following this protocol, researchers can reproducibly acquire high-quality imaging data to assess gene amplification.

Association between serum total cholesterol and the development of gastric cancer: A two-way two-sample Mendelian randomization study.

Previous epidemiologic studies have suggested a potential negative correlation between total cholesterol (TC) and Gastric cancer (GC); however, several observational studies have shown conflicting results and have failed to provide definitive evidence for a causal relationship between TC and GC. Therefore, we conducted a 2-sample bidirectional Mendelian randomization (MR) study to explore the genetic correlation and potential causal relationship between the 2 variables. We screened for single nucleotide polymorphisms (SNPs) associated with TC and GC utilizing a large-scale genome-wide association study (GWAS) public database. The causal relationship was analyzed using 5 MR analysis methods: inverse variance weighting (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. Additionally, reverse MR analysis was performed to evaluate the possibility of reverse causality. Sensitivity analyses were conducted, including heterogeneity tests, horizontal multiple validity tests, and leave-one-out tests. After meticulous screening, 79 SNPs were identified as instrumental variables (IVs). The IVW method revealed a causal relationship between TC and GC (OR = 0.844; 95% CI: 0.741-0.961; P = .01). Sensitivity analyses did not detect significant horizontal pleiotropy. Though heterogeneity was observed in the forward MR analysis (IVW, Qp = 0.0006), the results remained reliable as we utilized the IVW random-effects model as the primary analytical method. Furthermore, inverse MR analysis found no evidence of reverse causality between TC and GC, effectively ruling out the influence of GC on the reverse causality of TC. Our MR study provided evidence of a causal association between TC and GC, suggesting that TC acts as a protective factor against GC due to its negative association with the disease.

An analysis of the role of GAB2 in pan-cancer from a multidimensional perspective

BackgroundTo explore the role of GAB2 in pan-cancer based on bioinformatics analysis.MethodsBased on TCGA and GTEx databases, we used TIMER2.0 online analysis tool and R language to analyze the expression of GAB2 in pan-cancer. We used Kaplan–Meier Plotter to analyze the relationship between GAB2 and OS and RFS in pan-cancer. We utilized the CPTAC database to examine the expression of phosphorylated GAB2 in pan-cancer. We investigated the effects of mutation features on the occurrence and development of human cancers by cBioPortal and COSMIC. Using the database, we conducted an analysis of molecular compounds that have the potential to interact with GAB2 through molecular docking. Moreover, we use the TIMER to explore the relationship between GAB2 and immune cell infiltration, and draw relevant heatmaps by R language.ResultsGAB2 was abnormally expressed in various tumors and was associated with prognosis. There were differences in the expression of GAB2 phosphorylation in tumor tissues and corresponding normal tissues among different types of tumors. GAB2 interacts with Docetaxel and was associated with immune cell infiltration in various tumors.ConclusionGAB2 participates in regulating immune infiltration and affects the prognosis of patients. GAB2 may serve as a potential tumor marker.

TRIM59 deficiency promotes M1 macrophage activation and inhibits colorectal cancer through the STAT1 signaling pathway

Tumor-associated macrophages play a crucial role in the tumor microenvironment. Tripartite motif 59 (TRIM59), a member of the tripartite motif (TRIM) family, is known to be associated with immunological diseases and macrophage activation. The functional and molecular mechanisms by which TRIM59 affects the occurrence and development of colorectal cancer (CRC) through macrophages are still not well understood. To address this, we generated macrophage-specific TRIM59 conditional knockout mice and utilized these mice to establish colitis-associated cancer and MC38 transplanted CRC models for further investigation. We found that the deficiency of TRIM59 in macrophages inhibited colorectal tumorigenesis in mice. This tumor-suppressive effect was achieved by promoting the activation of M1 macrophages via STAT1 signaling pathway. Further mechanistic studies revealed that TRIM59 could regulate macrophage polarization by ubiquitinating and degrading STAT1. These findings provide evidence that TRIM59 deficiency promotes M1 macrophage activation and inhibits CRC through the STAT1 signaling pathway, suggesting that the TRIM59/STAT1 signaling pathway may be a promising target for CRC.

Extrachromosomal circular DNA promotes prostate cancer progression through the FAM84B/CDKN1B/MYC/WWP1 axis

BackgroundExtrachromosomal circular DNA (eccDNA), a kind of circular DNA that originates from chromosomes, carries complete gene information, particularly the oncogenic genes. This study aimed to examine the contributions of FAM84B induced by eccDNA to prostate cancer (PCa) development and the biomolecules involved.MethodsThe presence of eccDNA in PCa cells and the FAM84B transcripts that eccDNA carries were verified by outward and inward PCR. The effect of inhibition of eccDNA synthesis on FAM84B expression in PCa cells was analyzed by knocking down Lig3. The impact of FAM84B on the growth and metastases of PCa cells was verified by Cell Counting Kit-8 (CCK8), EdU, transwell assays, and a xenograft mouse model. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and dual-luciferase reporter assays were carried out to examine the effect of FAM84B/MYC on WWP1 transcription, and a co-immunoprecipitation (Co-IP) assay was conducted to verify the modification of CDKN1B by WWP1. The function of this molecular axis in PCa was explored by rescue assays.ResultsThe inhibited eccDNA synthesis significantly downregulated FAM84B in PCa cells, thereby attenuating the growth and metastasis of PCa. FAM84B promoted the transcription of WWP1 by MYC by activating the expression of MYC coterminous with the 8q24.21 gene desert in a beta catenin-dependent approach. WWP1 transcription promoted by MYC facilitated the ubiquitination and degradation of CDKN1B protein and inversely attenuated the repressive effect of CDKN1B on MYC expression. Exogenous overexpression of CDKN1B blocked FAM84B-activated MYC/WWP1 expression, thereby inhibiting PCa progression.ConclusionsFAM84B promoted by eccDNA mediates degradation of CDKN1B via MYC/WWP1, thereby accelerating PCa progression.

An Updated Review Summarizing the Anticancer Potential of Naringenin.

One important phytochemical is naringenin, which belongs to the flavanone class of polyphenols. It is found in citrus fruits, such as grapefruits, but it can also be found in tomatoes, cherries, and other food-grade medicinal plants. Naringenin has a significant chemotherapeutic promise, as several investigations have conclusively shown. Therefore, the goal of this review is to synthesize the literature that has been done on naringenin as a possible anti-cancer agent and clarify the mechanisms of action that have been described in treatment plans for different kinds of cancer. In a variety of cancer cells, naringenin works by affecting several pathways associated with cell cycle arrest, anti-metastasis, apoptosis, anti-angiogenesis, and DNA repair. It has been shown to alter several molecular targets linked to the development of cancer, such as drug transporters, transcription factors, reactive nitrogen species, reactive oxygen species, cellular kinases, and inflammatory cytokines and regulators of the cell cycle. In summary, this research provides significant insights into the potential of naringenin as a strong and prospective candidate for use in medicines, nutraceuticals, functional foods, and dietary supplements to improve the management of carcinoma.