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Neuroblastoma is the most common extracranial malignant tumor of childhood, accounting for 15% of all pediatric cancer deaths. Despite significant advances in our understanding of neuroblastoma biology, five-year survival rates for high-risk disease remain less than 50%, highlighting the importance of identifying novel therapeutic targets to combat the disease. MYCN amplification is the most frequent and predictive molecular aberration correlating with poor outcome in neuroblastoma. N-Myc is a short-lived protein primarily due to its rapid proteasomal degradation, a potentially exploitable vulnerability in neuroblastoma. AF1q is an oncoprotein with established roles in leukemia and solid tumor progression. It is normally expressed in brain and sympathetic neurons and has been postulated to play a part in neural differentiation. However, no role for AF1q in tumors of neural origin has been reported. In this study, we found AF1q to be a universal marker of neuroblastoma tumors. Silencing AF1q in neuroblastoma cells caused proteasomal degradation of N-Myc through Ras/ERK and AKT/GSK3β pathways, activated p53 and blocked cell cycle progression, culminating in cell death via the intrinsic apoptotic pathway. Moreover, silencing AF1q attenuated neuroblastoma tumorigenicity in vivo signifying AF1qs importance in neuroblastoma oncogenesis. Our findings reveal AF1q to be a novel regulator of N-Myc and potential therapeutic target in neuroblastoma.

Osteosarcoma(OS) is a highly aggressive bone cancer for which treatment has remained essentially unchanged for decades. Although OS is characterized by extensive genomic heterogeneity and instability, RB1 and TP53 have been shown to be the most commonly inactivated tumor suppressors in OS. We previously generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which largely recapitulates human OS with nearly complete penetrance. SKP2 is a repression target of pRb and serves as a substrate recruiting subunit of the SCFSKP2 complex. In addition, SKP2 plays a central role in regulating the cell cycle by ubiquitinating and promoting the degradation of p27. We previously reported the DKOAA transgenic model, which harbored a knock-in mutation in p27 that impaired its binding to SKP2. Here, we generated a novel p53-Rb1-SKP2 triple-knockout model (TKO) to examine SKP2 function and its potential as a therapeutic target in OS. First, we observed that OS tumorigenesis was significantly delayed in TKO mice and their overall survival was markedly improved. In addition, the loss of SKP2 also promoted an apoptotic microenvironment and reduced the stemness of DKO tumors. Furthermore, we found that small-molecule inhibitors of SKP2 exhibited anti-tumor activities in vivo and in OS organoids as well as synergistic effects when combined with a standard chemotherapeutic agent. Taken together, our results suggest that SKP2 inhibitors may reduce the stemness plasticity of OS and should be leveraged as next-generation adjuvants in this cancer.

The MYC oncogene is often dysregulated in human cancer, including hepatocellular carcinoma (HCC). MYC is considered undruggable to date. Here, we comprehensively identify genes essential for survival of MYChigh but not MYClow cells by a CRISPR/Cas9 genome-wide screen in a MYC-conditional HCC model. Our screen uncovers novel MYC synthetic lethal (MYC-SL) interactions and identifies most MYC-SL genes described previously. In particular, the screen reveals nucleocytoplasmic transport to be a MYC-SL interaction. We show that the majority of MYC-SL nucleocytoplasmic transport genes are upregulated in MYChigh murine HCC and are associated with poor survival in HCC patients. Inhibiting Exportin-1 (XPO1) in vivo induces marked tumor regression in an autochthonous MYC-transgenic HCC model and inhibits tumor growth in HCC patient-derived xenografts. XPO1 expression is associated with poor prognosis only in HCC patients with high MYC activity. We infer that MYC may generally regulate and require altered expression of nucleocytoplasmic transport genes for tumorigenesis.

TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression.

Breast cancer continues to be one of the most commonly diagnosed cancers around the world. Despite the decrease in mortality, there has been a steady increase in its incidence. There is much evidence that naturally occurring phytochemicals could prove to be safer alternatives aimed at prevention and development of breast cancer. In the present review, we discuss important phytochemicals, namely capsaicin, alpha-santalol and diallyl trisulphide that are shown to have chemopreventive and anti-tumour properties against breast cancer development. We examined current knowledge of their bioavailability, safety and modulation of molecular mechanisms including their ability to induce apoptotic cell death, promote cell cycle arrest, and inhibit cellular proliferation in different breast cancer cell lines and in vivo models. This review emphasises the importance of these naturally occurring phytochemicals and their potential of becoming therapeutic options in the arsenal against breast cancer development provided further scientific and clinical validation. [ABSTRACT FROM AUTHOR]

AbstractProfessional painters represent an occupational population group that deserves attention for study in the field of occupational toxicology due to the wide range of complex chemical mixtures they are exposed to. It is imperative to underscore that the International Agency for Research on Cancer has classified commercial painting as a high-risk occupation for the development of cancer. Given this context, the primary objective of the present study was to conduct a systematic review aimed at addressing the following question: are car painters at occupational risk regarding potential genotoxicity? To address this question, a selection process was undertaken, with three reviewers carefully selecting, reading, and analyzing full manuscripts from 26 studies included in this review. The technical rigor of these studies underwent meticulous scrutiny, culminating in the classification of six studies as Strong, eight as Moderate, and 12 as Weak, predicated on the extent of confounders considered. Taken together, the findings suggest that chemical substances from paints may indeed pose a risk of genotoxicity for professionals in this field, as all studies indicated genotoxicity among professional painters through various tests. [ABSTRACT FROM AUTHOR]

Background: Adenomatous polyposis coli (APC) gene, an oncogene, has been implicated in stomach adenocarcinoma (STAD), which is a common type of gastric cancer (GC). Although the relationship between APC gene mutations and gastric adenocarcinoma has been comprehensively studied, the potential role of these mutations in the prognosis and targeted therapy remains known. Methods: We utilized The Cancer Genome Atlas (TCGA) database to obtain gene expression matrices, clinical information, and mutation data from patients with STAD. The mutation status of the APC gene was analyzed, and its correlation with tumor mutational burden (TMB), microsatellite instability (MSI), and clinical prognosis in STAD was investigated. Gene set enrichment analysis (GSEA) was conducted to explore the pathological role of APC gene mutations in STAD metabolic pathways. Drug sensitivity analysis was conducted to identify potential targeted antitumor drugs for patients with APC gene mutations in gastric adenocarcinoma. Results: The results revealed that 88% (46/52) of STAD samples had nonsynonymous mutations. The mutation group exhibited a significantly higher TMB than the wild‐type group (p < 0.001), and the percentage of high MSI (MSI‐H) was significantly higher in the mutation group than in the wild‐type group (p < 0.001). Patients with APC mutations had a worse prognosis than those with APC wild‐type (p = 0.009). The APC gene mutation group displayed significant enrichment in amino acids, RNA, and several pathways (|NES| > 1 and nominal p value < 0.01). Compared to the wild‐type group, the mutation group exhibited a higher infiltration proportion of natural killer (NK) cells resting and eosinophils, whereas a lower infiltration proportion of monocytes and resting mast cells (p value < 0.05). AZD5991 exhibited significant sensitivity in patients with STAD carrying APC mutations (p = 0.028). Conclusion:APC gene mutations play a crucial role in the prognosis, molecular characteristics, and potential therapeutic strategies for gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

From its earliest characterization, it has been recognized that there is a role for regulated (programmed) cell death in cancer. As our understanding of the different types of programmed cell death processes and their molecular control has advanced, so have the technologies that allow us to manipulate these processes to, for example, fight against cancer. In this review, we describe the roles of the different forms of regulated cell death in the development of cancer as well as their potential therapeutic exploitation. In that vein, we explore the development and use of BH3-mimetics, a unique class of drugs that can directly activate the apoptotic cell death machinery to treat cancer. Finally, we address key challenges that face the field to improve the use of these therapeutics and the efforts that are being undertaken to do so. In this review, La Marca et al. delve into the role of cell death in tumorigenesis; particularly apoptosis, but also touching on emerging roles for other cell death variants. The review also discusses the development, limitations, and future of BH3-mimetics, the most clinically advanced class of compounds for direct apoptosis induction. [ABSTRACT FROM AUTHOR]

Since suppressor/enhancer of Lin‐12‐like (SEL1L) was cloned in 1997, various pieces of evidence from lower species suggest it plays a significant role in protein degradation via the ubiquitin‐proteasome system. The relevance of SEL1L in many aspects of malignant transformation and tumorigenic events has been the subject of research, which has shown compelling in vitro and in vivo findings relating its altered expression to changes in tumor aggressiveness. The Endoplasmic Reticulum (ER) in tumor cells is crucial for preserving cellular proteostasis by inducing the unfolded protein response (UPR), a stress response. A crucial component of the UPR is ER‐associated degradation (ERAD), which guards against ER stress‐induced apoptosis and the removal of unfolded or misfolded proteins by the ubiquitin‐proteasome system. As a protein stabilizer of HMG‐CoA reductase degradation protein 1 (HRD1), one of the main components of ERAD, SEL1L plays an important role in ER homeostasis. Notably, the expression levels of these two proteins fluctuate independently in various cancer types, yet changes in their expression affect the levels of other associated proteins during cancer pathogenesis. Recent studies have also outlined the function of SEL1L in cancer medication resistance. This review explores the value of targeting SEL1L as a novel treatment approach for cancer, focusing on the molecular processes of SEL1L and its involvement in cancer etiology. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial. Methods: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer. Results: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e., AUC: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive. Conclusion: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis. [ABSTRACT FROM AUTHOR]

Garcinia kola is a medicinal food commonly consumed in Sub-Sahara Africa, for which Kolaviron (KV) is the active portion. As a follow-up to our earlier chemopreventive studies, we investigated the chemotherapeutic effects of KV on experimentally induced mammary carcinogenesis in female Wistar rats. Mammary carcinogenesis was induced using 80 mg/kg of 7,12-dimethylbenzanthracene (DMBA) administered by oral gavage. One hundred-fifty days post-DMBA induction, estrogen receptor-α (ER-α) levels were determined in the experimental rats before treatment with KV commenced. Treatment was done using 50, 100, and 200 mg/kg KV thrice a week for 4 weeks, after which the experiment was terminated. Significantly higher levels of estrogen receptor-α, CYP 1A1, malondialdehyde, formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased cytokine (interleukin-6 and tumor necrosis factor-α) activity were observed in DMBA-induced rats, which were attenuated in KV-treated rats. Tyrosine metabolism was exclusively enriched in DMBA-induced rats in contrast to KV-treated rats. Collectively, the results point to the chemotherapeutic potential of KV. [ABSTRACT FROM AUTHOR]

Somatic mutations in genes encoding components of the RNA splicing machinery occur frequently in multiple forms of cancer. The most frequently mutated RNA splicing factors in cancer impact intronic branch site and 3′ splice site recognition. These include mutations in the core RNA splicing factor SF3B1 as well as mutations in the U2AF1/2 heterodimeric complex, which recruits the SF3b complex to the 3′ splice site. Additionally, mutations in splicing regulatory proteins SRSF2 and RBM10 are frequent in cancer, and there has been a recent suggestion that variant forms of small nuclear RNAs (snRNAs) may contribute to splicing dysregulation in cancer. Here, we describe molecular mechanisms by which mutations in these factors alter splice site recognition and how studies of this process have yielded new insights into cancer pathogenesis and the molecular regulation of splicing. We also discuss data linking mutant RNA splicing factors to RNA metabolism beyond splicing. Mutations in genes encoding components of the RNA splicing machinery occur frequently in multiple cancers. This review describes the molecular mechanisms by which cancer-associated mutations in splicing factors alter splice site recognition and how studies of this process have yielded new insights into cancer pathogenesis and the molecular regulation of splicing. [ABSTRACT FROM AUTHOR]

Assess rates of true pseudoprogression in unconfirmed progressive disease (iUPD) in a pool of immunotherapy clinical trials for different cancers, analyze tumor characteristics that drive iUPD classification, and investigate potentials predictors of pseudoprogression. Retrospective interpretation of prospectively acquired data. Patients from 18 immunotherapy clinical trials with two arms (RECIST 1.1, iRECIST), of 10 cancer types were selected. Pooled rate of true pseudoprogression among iUPD was estimated using a common effect meta-analysis. Target, Non-target, and new lesions as the trigger of confirmed-vs pseudo-progression were compared using Chi-Square and Fisher exact tests. Conditional logistic regression was used to investigate the association between age, sex, tumor burden at baseline, and number of follow ups and pseudoprogression. 60/287 (21%) patients (17 women) were classified as iUPD with at least one subsequent confirmatory timepoint. The overall pooled estimate of pseudoprogression was 15% (95%CI: 8%–-26%). Nontarget lesions were significantly more frequent the cause of iUPD than change in Target lesions size (p < 0.001). Most observations of true pseudoprogression occurred in the first follow-up (77%), whereas confirmed progression occurred in later time points during the trial. Pseudoprogression was not significantly associated with age, sex, tumor burden at baseline, or number of timepoints. In a pool of immunotherapy trials, the rate of true pseudoprogression was 15%, most often in the first timepoint after baseline than later in treatment. iUPD categorization was mostly driven by changes in NT lesions rather than objective changes in measurements of target lesions. • Considering trials size and proportions, the pooled estimate of true pseudoprogression was 15% (95%CI: 8%–26%). • Confirmed progression and pseudoprogression were mainly driven by change in Non-target lesions than size of target lesions. • Pseudoprogression occurred most often in the first follow-up after baseline than true progression. [ABSTRACT FROM AUTHOR]

Regular exercise is believed to suppress cancer progression. However, the precise molecular mechanisms by which exercise prevents cancer development remain unclear. In this study, using a steatosis‐associated liver cancer mouse model, we found that regular exercise at a speed of 18 m/min for 20 min daily suppressed liver cancer development. To explore the underlying mechanisms, we examined the gene expression profiles in the livers of the exercise and non‐exercise groups. The expressions of circadian genes, such as Per1 and Cry2, were upregulated in the exercise group. As circadian rhythm disruption is known to cause various diseases, including cancer, improving circadian rhythm through exercise could contribute to cancer prevention. We further found that the expression of a series of E2F1 and c‐Myc target genes that directly affect the proliferation of cancer cells was downregulated in the exercise group. However, the expression of E2F1 and c‐Myc was transcriptionally unchanged but degraded at the post‐translational level by exercise. Cry2, which is regulated by the Skp1‐Cul1‐FBXL3 (SCFFBXL3) ubiquitin ligase complex by binding to FBXL3, can form a complex with E2F1 and c‐Myc, which we think is the mechanism to degrade them. Our study revealed a previously unknown mechanism by which exercise prevents cancer development. [ABSTRACT FROM AUTHOR]

Objectives. Emmprin (CD147/BSG) protein is estimated to play a key role in cell migration and chemoresistance in viral carcinogenesis. However, there are very limited studies investigating the CD147 in the oncogenesis of Kaposi's sarcoma-associated herpesvirus. This study aims to reveal the relationship between CD147 expression with histopathological parameters, disease pattern, and recurrence in Kaposi's sarcoma (KS). Methods. The study included 67 patients diagnosed with KS between January 1982 and September 2023. Clinical and histopathological features were analyzed retrospectively. HHV-8, CD31, and CD147 expressions were evaluated by immunohistochemistry. Results. Sixteen (24%) female and 51 (76%) male patients with median age of 64 (10-86) were included in the study. CD147 was positive in 57 (85%) cases and associated with nodular pattern (P =.001), presence of solid/fibrosarcomatous area (P =.005), and high mitotic activity (P =.035). The disease relapsed in 17 (27%) of the 63 patients with median 2 (0-12) years follow-up. While a 5-year relapse-free survival was 48.5% in the CD147 diffuse positive group, it was 83.4% in focal positive and 100% in negative cases (P =.029). Conclusion. Our study exhibited the relationship between CD147 overexpression and recurrence in KS, but the inhomogeneity of the treatment groups and the small number of patients should also be considered. These findings may provide insight into the pathogenesis of KS and the development of targeted therapies in the future. [ABSTRACT FROM AUTHOR]

The study aims to evaluate the performance of Vitamin D/calcitriol-induced miR-589-3p in predicting the prognosis of cervical cancer patients and its role in cancer cell function. To identify differentially expressed miRNAs (DEMs) related to calcitriol treatment, the GSE61829 dataset was analyzed. MiR-589-3p expression levels were verified in cervical cancer patients. The association of miR-589-3p with overall survival was investigated using Kaplan-Meier survival analyses and the multi-variate Cox proportional hazards model analysis. The effects of miR-589-3p on cervical cancer cells and calcitriol-treated cells were examined using the MTT assay and Transwell migration/invasion assay. From GSE61829 dataset, a total of eleven DEMs were identified, including miR-589-3p. MiR-589-3p was found to be decreased in cervical cancer but increased after one-year intake of Vitamin D. Low miR-589-3p after one-year intake of Vitamin D was identified as a predictive factor for low survival probability (p = 0.0059) with a significant impact on the death risk (HR: 3.04; 95%CI: 1.47-6.29; p = 0.003). MiR-589-3p overexpression inhibited the proliferation and migration/invasion of cervical cancer cells and calcitriol-treated cervical cancer cells. In conclusion, miR-589-3p can be induced by Vitamin D/calcitriol treatment and inhibit cervical cancer progression. MiR-589-3p has the potential to predict overall survival in patients with cervical cancer. [ABSTRACT FROM AUTHOR]

In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3. [ABSTRACT FROM AUTHOR]

Purpose: This study performed a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationships of C-reactive protein and 41 inflammatory regulators with melanoma, including data from UK Biobank, Cardiovascular Risk in Young Finns Study, and Cohorts for Inflammation Work Group. Methods: We selected the inverse variance weighting (IVW) to merge the estimated causal effects of multiple SNPs into a weighted average. To evaluate the heterogeneities of IVW, the Cochran Q statistic, and I2 index were used. What's more, several sensitivity analyses were employed, including IVW, MR-Egger, weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO). Results: With SNPs reaching P < 5 × 10−8, the analyses findings revealed that IL-16 had a significant positively association with genetically risk of melanoma (ORIVW: 1.05; 95% CI: 1.03–1.07; P < 0.001), and high levels of MCP1 (ORIVW: 1.13; 95% CI: 1.03–1.23; P = 0.01) were suggestively associated with melanoma susceptibility. What's more, TNF-β (ORIVW: 1.07; 95% CI: 1.01–1.13; P = 0.02) and IL-8 (ORIVW: 1.08, 95% CI: 1.01–1.16; P = 0.03) were demonstrated a positive association with the risk of melanoma under a less stringent cut-off (P < 5 × 10−6). Conversely, we found a facilitative effect of melanoma susceptibility on IP-10 and inhibitory effects on IL-6, IL-1b, and GRO-α. Conclusion: The genetic evidence that we have uncovered indicates a potential association between the levels of specific inflammatory markers (IL-16, IL-8, MCP-1, and TNF-β) and the risk of melanoma. Further research is imperative to translate these findings into clinical applications. [ABSTRACT FROM AUTHOR]

Objectives: Oxidative stress, an imbalance between the body's natural antioxidant defenses and the production of reactive oxygen species (ROS), can result in serious oral diseases, including oral cancer, periodontal diseases, and oral lichen planus, through the activation of the redox‐sensitive transcription factors and inflammation. The purpose of this study was to assess the potential effects of a removable complete denture on the levels of oxidative stress markers, such as lipid peroxidation (MDA), advanced oxidation protein products (AOPP), and catalase, and the quantitative expression of the redox‐sensitive transcription factor NF‐κB p65 subunit. Materials and Methods: This interventional follow‐up study enrolled 40 participants of both sexes aged 28–78 years, with a median age of 56 years, where unstimulated saliva was collected before denture placement, immediately after the denture placement, and 24 h, 7 days, and 30 days after the denture placement. The most prominent ROS overproduction was reported on the seventh day (p < 0.05), followed by a significant fall in antioxidative defense. Results: The NF‐κB p65 subunit, whose expression pattern was highest in the same time period on the seventh day, serves as a signaling molecule for redox imbalance due to ROS production. Over the next 30 days, its levels remained moderately increased compared to the basal value, which may influence pro‐inflammatory pathways and the integrity of oral tissue components. These alterations may be induced by the dentures, which can produce high pressures on the supporting tissues or by the synthetic materials used for producing the dentures. Conclusion: Our research may help to clarify the potential pathways by which oxidative stress and redox‐sensitive inflammatory mediators, as well as mechanical and chemical irritants, may serve as risk factors for premalignant lesions in the mouth. Further research on this topic is required to understand the molecular mechanisms behind the relationship between inflammation and oral premalignant lesions caused by mechanical and chemical irritation. [ABSTRACT FROM AUTHOR]

The emergence of 16S rRNA and metagenomic sequencing has gradually revealed the close relationship between dysbiosis and colorectal cancer (CRC). Recent studies have confirmed that intestinal dysbiosis plays various roles in the occurrence, development, and therapeutic response of CRC. Perturbation of host immunity is one of the key mechanisms involved. The intestinal microbiota, or specific bacteria and their metabolites, can modulate the progression of CRC through pathogen recognition receptor signaling or via the recruitment, polarization, and activation of both innate and adaptive immune cells to reshape the protumor/antitumor microenvironment. Therefore, the administration of gut bacteria to enhance immune homeostasis represents a new strategy for the treatment of CRC. In this review, we cover recent studies that illuminate the role of gut bacteria in the progression and treatment of CRC through orchestrating the immune response, which potentially offers insights for subsequent transformative research. [ABSTRACT FROM AUTHOR]

Low‐grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high‐risk human papillomavirus (HR‐HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community‐based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed‐up at 6, 12, and 24 months, post‐diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1‐hydroxipayrene (1‐OHP) level. Our results showed that the 1‐OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P <.05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24–2.67), (1.98, 1.42–2.75), and (2.37, 1.61–3.49) at 6, 12, and 24 months, post‐diagnosis, respectively. The effect was enhanced with HR‐HPV positivity, as determined at 6 (1.82, 1.24–2.67), 12 (3.02, 1.74–5.23), and 24 (2.51, 1.48–4.26) months, post‐diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR‐HPV‐positive patients than in HR‐HPV‐negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR‐HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) represents the most prevalent internal and reversible modification on RNAs. Different cell types display their unique m6A profiles, which are determined by the functions of m6A writers and erasers. M6A modifications lead to different outcomes such as decay, stabilization, or transport of the RNAs. The m6A-encoded epigenetic information is interpreted by m6A readers and their interacting proteins. M6A readers are essential for different biological processes, and the defects in m6A readers have been discovered in diverse diseases. Here, we review the latest advances in the roles of m6A readers in development and diseases. These recent studies not only highlight the importance of m6A readers in regulating cell fate transitions, but also point to the potential application of drugs targeting m6A readers in diseases. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) are a distinct class of RNAs with longer than 200 base pairs that are not translated into proteins. Small Nucleolar RNA Host Gene 3 (SNHG3) is a lncRNA and frequently dysregulated in various human cancers. Objective: This review provides a comprehensive analysis of current research on lncRNA SNHG3, focusing on its role within the competitive endogenous RNA (ceRNA) network and its implications in cancer. Methods: A systematic literature review was conducted using PubMed up to October 2023. The search strategy included keywords such as "lncRNA SNHG3", "competitive endogenous RNA", "cancer", and related terms. Studies were selected based on relevance to SNHG3's involvement in cancer pathogenesis and progression. Results: Disruptions in the ceRNA network involving lncRNA SNHG3 can impair normal cell growth and differentiation, significantly contributing to disease pathogenesis, particularly cancer. This review highlights SNHG3's substantial impact on various cancer processes and its potential as a diagnostic and therapeutic tool for aggressive cancers. Conclusion: The findings underscore SNHG3's pivotal role in cancer prevention, diagnosis, and treatment, laying a foundation for future research in cancer management. Insights from this review emphasize the necessity for further exploration and development of SNHG3-based diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Endothelial cell specific-1 (ESM-1), also known as endocan, is a soluble dermatan sulfate proteoglycan that is mainly secreted by endothelial cells. Endocan is associated with tumorigenesis and cancer progression and is also related to cardiovascular disorders, autoimmune diseases, and sepsis. The phenylalaninerich region and linear polysaccharide of endocan are necessary for the protein to exert its biological functions. Elevated plasma endocan levels reflect endothelial activation and dysfunction. In addition, endocan participates in complex inflammatory responses and proliferative processes. Here, we reviewed current research on endocan, elaborated the protein's structure and biological functions, and speculated on its possible clinical value in nervous system diseases. We conclude that endocan may be a glycoprotein that plays an important role in neurological disorders. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a commonly occurring malignancy in elderly men. Olaparib, a poly ADP-ribose polymerase inhibitor, is utilized in PCa treatment. However, patients often develop resistance to olaparib after a period of treatment. Genetic alterations may play a significant role in this resistance, but the specific genes involved remain unclear. This study collected RNA-sequence data from the Gene Expression Omnibus database on both olaparib-sensitive and -resistant PCa cells to identify genes crucial for resistance. Subsequently, the enriched pathways of these genes were analyzed, and a protein–protein interaction (PPI) network was constructed to identify hub genes. The effect of these hub genes on PCa occurrence, progression, and prognosis was assessed using data from The Cancer Genome Atlas and Chinese Prostate Cancer Genome and Epigenome Atlas databases. Finally, this study validated our findings in clinical PCa samples and cells. From the GSE189186 dataset, 50 upregulated genes and 2 downregulated genes were identified in olaparib-resistant C4-2B and LNCaP cells. Utilizing the PPI network, eight upregulated genes (BBC3, TP53I3, FDXR, DDB2, CDKN1A, GADD45A, ZMAT3, and SESN1) were identified as hub genes for olaparib-resistant PCa cells. Furthermore, some of these genes were central to PCa occurrence, with BBC3 also influencing progression and prognosis. Importantly, BBC3 expression was upregulated in clinical PCa samples and affected PCa cells sensitive to olaparib, suggesting its potential as a predictive marker for PCa development and olaparib resistance. [ABSTRACT FROM AUTHOR]

Background: Chemoresistance of cancer cells, resulting from various mechanisms, is a significant obstacle to the effectiveness of modern cancer therapies. Targeting fibroblast growth factors (FGFs) and their receptors (FGFRs) is becoming crucial, as their high activity significantly contributes to cancer development and progression by driving cell proliferation and activating signaling pathways that enhance drug resistance. Methods: We investigated the potential of honokiol and FGF ligand trap in blocking the FGF1/FGFR1 axis to counteract drug resistance. Using PEAQ-ITC, we verified direct interaction of honokiol with the FGFR1 kinase domain. We then demonstrated the effect of FGF1/FGFR1 inhibition on taltobulin resistance in cells expressing FGFR1. Finally, we generated drug-resistant clones by prolonged exposure of cells with negligible FGFR levels to taltobulin alone, taltobulin and honokiol, or taltobulin and FGF ligand trap. Results: We demonstrated for the first time a direct interaction of honokiol with the FGFR1 kinase domain, resulting in inhibition of downstream signaling pathways. We revealed that both honokiol and FGF ligand trap prevent FGF1- dependent protection against taltobulin in cancer cells expressing FGFR1. In addition, we showed that cells obtained by long-term exposure to taltobulin are resistant to both taltobulin and other microtubule-targeting drugs, and exhibit elevated levels of FGFR1 and cyclin D. We also found that the presence of FGFligand trap prevents the development of long-term resistance to taltobulin. Conclusion: Our results shed light on how blocking the FGF1/FGFR1 axis by honokiol and FGF ligand trap could help develop more effective cancer therapies, potentially preventing the emergence of drug-resistant relapses. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Deubiquitinating enzymes (DUBs) have emerged as critical regulators of protein ubiquitination and proteasomal degradation, influencing various cellular processes relevant to cancer pathogenesis. In this study, the research progress between ovarian cancer and DUBs was mapped and visualized using bibliometrics, and the expression patterns and biological roles of DUBs in ovarian cancer were summarized. Methods: Studies related to DUBs in ovarian cancer were extracted from the Web of Science Core Collection (WoSCC) database. VOSviewer 1.6.20, CiteSpace 6.3.R1, and R4.3.3 were used for bibliometric analysis and visualization. Results: For analysis 243 articles were included in this study. The number of publications on DUBs in ovarian cancer has gradually increased each year. China, the United States, and the United Kingdom are at the center of this field of research. The Johns Hopkins University, Genentech, and Roche Holding are the main research institutions. David Komander, Zhihua Liu, and Richard Roden are the top authors in this field. The top five journals with the largest publication volumes in this field are Biochemical and Biophysical Research Communications, Journal of Biological Chemistry, PLOS One, Nature Communications, and Oncotarget. Keyword burst analysis identified five research areas: "deubiquitinating enzyme," "expression," "activation," "degradation," and "ubiquitin." In addition, we summarized the expression profiles and biological roles of DUBs in ovarian cancer, highlighting their roles in tumor initiation, growth, chemoresistance, and metastasis. Conclusion: An overview of the research progress is provided in this study on DUBs in ovarian cancer over the last three decades. It offers insight into the most cited papers and authors, core journals, and identified new trends. [ABSTRACT FROM AUTHOR]

Background: Evaluation of indeterminate pulmonary nodules (IPNs) often creates a diagnostic conundrum which may delay the early detection of lung cancer. Rare circulating genetically abnormal cells (CGAC) have previously demonstrated utility as a biomarker for discriminating benign from malignant small IPNs in the LungLB assay. CGAC are identified using a unique 4-color fluorescence in-situ hybridization (FISH) assay and are thought to reflect early cell-based events in lung cancer pathogenesis and the anti-tumor immune response. LungLB is a prognostic tool that combines the CGAC biomarker and clinical features to aid in IPN evaluation by improving the stratification of patient risk of malignancy. Methods: Herein we describe the analytical performance of the LungLB blood test. Analytical validation was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines with adaptations for rare cell-based assays. Multiple operators, reagent lots, and assay runs were tested to examine accuracy, precision, reproducibility, and interfering factors. Results: The FISH probes used in the LungLB assay demonstrate 100% sensitivity and specificity for their intended chromosomal loci (3q29, 3p22.1, 10q22.3 and 10cen). LungLB demonstrates analytical sensitivity of 10 CGAC per 10,000 lymphocytes analyzed, 100% analytical specificity, and high linearity (R2 = 0.9971). Within run measurements across 100 samples demonstrated 96% reproducibility. Interfering factors normally found in blood (lipemia, biotin) and exposure to adverse temperatures (-20ºC or 37ºC) did not interfere with results. Sample stability was validated to 96 hours. Conclusion: The analytical performance of LungLB in this validation study successfully demonstrates it is robust and suitable for everyday clinical use. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) has become the most prevalent cancer worldwide, and further research is being conducted to deepen our understanding of its pathogenesis and treatment. Lipid metabolism disorder is a significant alteration in cancer cells, and the investigation into the role of Interleukin‐17 (IL‐17) in malignant tumors has emerged as a research focus in recent years. Thus, exploring changes in lipid metabolism and inflammatory factors in BC cells is crucial in identifying potential therapeutic targets. This article summarizes the progress made in the research on the main low‐density cholesterol (LDL) transporter and IL‐17 in lipid metabolism, and their potential involvement in the development of BC. The article aims to establish a theoretical foundation for the development of BC‐related therapies. [ABSTRACT FROM AUTHOR]

CoQ10 (Coenzyme Q10) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ10 is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ10 and UBIAD1 states impair ECM (extracellular matrix)-mediated oncogenic signaling and reduce ferroptosis resistance in BC settings. Analyses on human patients and mouse models reveal that UBIAD1 loss is associated with BC development and progression and UBIAD1 expression in BC limits CTCs (circulating tumor cells) survival and lung metastasis formation. Overall, this study reveals that CoQ10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis. The roles of CoQ10 and producing enzymes in cancer have not been well explored. Here, the authors identify that the CoQ10-biosynthetic enzyme UBIAD1 is a tumor suppressor in breast cancer. CoQ10 induced alterations in plasma membrane mechanical properties lead to increased cellular stiffness and impaired tumorigenic signaling, as well as enhanced sensitivity to ferroptosis. [ABSTRACT FROM AUTHOR]

Human Carbonic Anhydrases (hCA) are enzymes that contribute to cancer's development and progression. Isoforms IX and XII have been identified as potential anticancer targets, and, more specifically, hCA IX is overexpressed in hypoxic tumor cells, where it plays an important role in reprogramming the metabolism. With the aim to find new inhibitors towards IX and XII isoforms, the hybridization of the privileged scaffolds isatin, dihydrothiazole, and benzenesulfonamide was investigated in order to explore how it may affect the activity and selectivity of the hCA isoforms. In this respect, a series of isatin thiazolidinone hybrids have been designed and synthesized and their biological activity and selectivity on hCA I, hCA II, hCA IX, and hCA XII explored. The new compounds exhibited promising inhibitory activity results on isoforms IX and XII in the nanomolar range, which has highlighted the importance of substituents in the isatin ring and in position 3 and 5 of thiazolidinone. In particular, compound 5g was the most active toward hCA IX, while 5f was the most potent inhibitor of hCA XII within the series. When both potency and selectivity were considered, compound 5f appeared as one of the most promising. Additionally, our investigations were supported by molecular docking experiments, which have highlighted the putative binding poses of the most promising compound. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to determine the gene expression profiles associated with chemotherapeutic responses in conventional osteosarcomas (COS) within South Africa. We observed a significant downregulation in the ATP binding cassette subfamily C members (ABCC3 and ABCB1-p-glycoprotein), excision repair cross-complimenting group 1 (ERCC 1), replication factor C subunit 1 (RFC1), and tumour protein 53 (p53) genes in the COS tumours compared to the healthy donors. Furthermore, an upregulated ERCC1 gene expression level predicted a poor chemotherapeutic response. Additionally, the predictors of COS chemotherapeutic response comprised age, chondroblastic and osteoblastic histological subtypes, and ABCC3, ERCC1, and RFC1 gene expression. Background: We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa. Materials and methods: In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2−∆∆CT method to determine the fold change in gene expression alongside GAPDH (housekeeping gene). Results: We observed a significant downregulation in the mRNA expression profiles of ABCB1-p-glycoprotein (p = 0.0007), ABCC3 (p = 0.002), ERCC1 (p = 0.007), p-53 (p = 0.007), and RFC1 (p = 0.003) in the COS patients compared to the healthy donors. Furthermore, ABCB1-p-glycoprotein (p = 0.008) and ABCC3 (p = 0.020) exhibited a significant downregulation in the COS tumour tissues when compared to the healthy donors. In our univariate logistic regression, the predictors of chemotherapeutic response comprised ERCC1 [restricted cubic spline (RCS) knot: OR −0.27; CI −0.504 to −0.032; p = 0.036]; osteoblastic subtype [OR −0.36; CI −0.652 to −0.092; p = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; p < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; p = 0.032]. In our multivariable logistic regression, the significant predictors of chemotherapeutic response comprised age [RCS knot: OR −2.5; CI −3.616 to −1.378; p = 0.022]; ABCC3 [RCS knot: OR 0.67; CI 0.407 to 0.936, p = 0.016]; ERCC1 [RCS knot: OR 0.57; CI 0.235 to 0.901; p = 0.044]; RFC1 [RCS knot: OR −1.04; CI −1.592 to −0.487; p = 0.035]; chondroblastic subtype [OR −0.83; CI −1.106 to −0.520; p = 0.012]; and osteoblastic subtype [OR −1.28; CI −1.664 to −0.901; p = 0.007]. Conclusions: In this South African cohort, we observed the unique gene expression profiles of osteosarcoma tumourigenesis and chemotherapeutic responses. These may serve as prognostication and therapeutic targets. Larger-scale research is needed on the African continent. [ABSTRACT FROM AUTHOR]

Simple Summary: Currently, delivering nanoparticles to hard-to-reach tumor sites remains a challenge in nanomedicine. Mesenchymal stem cells are an innovative strategy for targeting tumors, and genetic engineering could enable them to release antitumor agents and/or nanomaterials at tumor sites. Therefore, combining radiosensitizing agents with mesenchymal stem cells represents a promising strategy in the fight against cancer. Still, evaluating whether nanoparticles can modulate mesenchymal stem cells' behavior is essential. This study assessed the impact of new Fe3O4@Au nanoparticles on human pulmonary mesenchymal stem cells to determine whether they can be used as carriers for radiosensitizer agents to cancer sites. This study focused on the markers related to cell death, redox and proinflammatory status, and tumorigenesis. Background/Objectives: Metallic nanoparticles (NPs) exhibit interesting radiosensitizing effects, and finding a way to accurately deliver them appears to be crucial. Due to their tumor tropism, mesenchymal stem cells (MSCs) represent a strategic approach. Therefore, we aimed to evaluate the impact of core–shell Fe3O4@Au NPs on the functionality of human pulmonary MSCs (HPMSCs). Methods/Results: The results showed that 100 µg/mL Fe3O4@Au NPs, accumulated in HPMSCs (revealed by Prussian blue staining), did not alter cell viability as assessed by cell counting, MTT, and LDH assays. However, caspase 9 and Bcl2 gene expression, evaluated by RT-qPCR, was regulated 72 h after exposure to the NPs. Moreover, the NPs also decreased proinflammatory cytokine/chemokine secretions, except for CXCL8 (ELISA). These modulations were associated with the downregulation of AMPK gene expression at 24 h. In contrast, the NPs did not modulate VEGF, PI3K, or PDGF gene expression. Nevertheless, a decrease in VEGF secretion was observed after 24 h of exposure to the NPs. Interestingly, the Fe3O4@Au NPs did not modulate Nrf2 gene expression, but they did regulate the expression of the genes encoding Nox4 and HMOX-1. Additionally, the NPs increased ROS production, suggesting a redox imbalance. Conclusions: Finally, the Fe3O4@Au NPs did not affect the HPMSCs' viability or proangiogenic/tumorigenic markers. These findings are encouraging for investigating the effects of Fe3O4@Au NPs delivered by HPMSCs to tumor sites in combination with radiation. [ABSTRACT FROM AUTHOR]

Simple Summary: We provide a historical perspective on the current concepts of minimal residual disease (MRD) and how it evolves from minimal residual disease to measurable residual disease. We aim to highlight the fundamental biology behind MRD—the overlap between leukemia stem cells and MRD, and the role of the bone marrow microenvironment in the persistence of MRD. We describe how our success in measuring and subsequently eliminating residual disease in acute promyelocytic leukemia will pave the way towards progress in other acute leukemias. Introduction: Advances in molecular biology, polymerase chain reaction (PCR), and next-generation sequencing (NGS) have transformed the concept of minimal residual disease (MRD) from a philosophical idea into a measurable reality. Current Treatment Paradigms and Lessons Learned from APL: Acute promyelocytic leukemia (APL) leads the way in this transformation, initially using PCR to detect MRD in patients in remission, and more recently, aiming to eliminate it entirely with modern treatment strategies. Along the way, we have gained valuable insights that, when applied to other forms of acute leukemia, hold the potential to significantly improve the outcomes of these challenging diseases. Does the BM Microenvironment Play a Role in MRD?: In this review, we explore the current use of MRD in the management of acute leukemia and delve into the biological processes that contribute to MRD persistence, including its overlap with leukemia stem cells and the role of the bone marrow microenvironment. [ABSTRACT FROM AUTHOR]

Simple Summary: MicroRNAs (miRNAs) play a significant role in the initiation and progression of colorectal cancer and are extensively well-studied in this context. However, the interplay between miRNAs and RNA-binding proteins, especially HuR, is yet to be fully understood. In this review, we summarize the regulatory role of the HuR-miRNA axis in colorectal cancer, highlighting its importance for an improved diagnostic or prognostic approach. Colorectal cancer (CRC) remains a significant global health burden with high incidence and mortality. MicroRNAs (miRNAs) are small non-protein coding transcripts, conserved throughout evolution, with an important role in CRC tumorigenesis, and are either upregulated or downregulated in various cancers. RNA-binding proteins (RBPs) are known as essential regulators of miRNA activity. Human antigen R (HuR) is a prominent RBP known to drive tumorigenesis with a pivotal role in CRC. In this review, we discuss the regulatory role of the HuR/miRNA axis in CRC. Interestingly, miRNAs can directly target HuR, altering its expression and activity. However, HuR can also stabilize or degrade miRNAs, forming complex feedback loops that either activate or block CRC-associated signaling pathways. Dysregulation of the HuR/miRNA axis contributes to CRC initiation and progression. Additionally, HuR-miRNA regulation by other small non-coding RNAs, circular RNA (circRNAs), or long-non-coding RNAs (lncRNAs) is also explored here. Understanding this HuR-miRNA interplay could reveal novel biomarkers with better diagnostic or prognostic accuracy. [ABSTRACT FROM AUTHOR]

Simple Summary: End-stage renal disease (ESRD) is a life-threatening condition that necessitates renal replacement therapies such as dialysis. ESRD is believed to increase cancer risk and cancer mortality rate; however, data on cancer risk and cancer-specific mortality in patients with ESRD present multiple statistical issues, including sampling errors, bias, and confounding factors, falsely depicting high cancer incidence. Only renal cell and urothelial cancers are driven by ESRD. However, cancer-specific mortality is generally lower in patients with ESRD than in the general population, which corresponds to the fact that cancers arising from ESRD are generally less aggressive and have low metastatic potential. ESRD damages not only normal but also malignant cells in multiple stages of cancer development. This review highlights the potential anticancer effects of ESRD, proposing a reconsideration of the hypothesis that ESRD promotes cancer development and progression. The prevalence of end-stage renal disease is increasing worldwide. Malignancies accompanying end-stage renal disease are detected in approximately 120 individuals per 10,000 person-years. Most studies have suggested that end-stage renal disease causes carcinogenesis and promotes tumor development; however, this theory remains questionable. Contrary to the theory that end-stage renal disease is predominantly carcinogenic, recent findings have suggested that after controlling for biases and sampling errors, the overall cancer risk in patients with end-stage renal disease might be lower than that in the general population, except for renal and urothelial cancer risks. Additionally, mortality rates associated with most cancers are lower in patients with end-stage renal disease than in the general population. Several biological mechanisms have been proposed to explain the anticancer effects of end-stage renal disease, including premature aging and senescence, enhanced cancer immunity, uremic tumoricidal effects, hormonal and metabolic changes, and dialysis therapy-related factors. Despite common beliefs that end-stage renal disease exacerbates cancer risk, emerging evidence suggests potential tumor-suppressive effects. This review highlights the potential anticancer effects of end-stage renal disease, proposing reconsideration of the hypothesis that end-stage renal disease promotes cancer development and progression. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that the passenger strands microRNAs (miRNAs) derived from pre-miRNAs are closely involved in cancer pathogenesis. Analysis of our miRNA expression signature of lung adenocarcinoma (LUAD) and The Cancer Genome Atlas (TCGA) data revealed that miR-144-5p (the passenger strand derived from pre-miR-144) was significantly downregulated in LUAD tissues. The aim of this study was to identify therapeutic target molecules controlled by miR-144-5p in LUAD cells. Ectopic expression assays demonstrated that miR-144-5p attenuated LUAD cell aggressiveness, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. A total of 18 genes were identified as putative cancer-promoting genes controlled by miR-144-5p in LUAD cells based on our in silico analysis. We focused on a family with sequence similarity 111 member B (FAM111B) and investigated its cancer-promoting functions in LUAD cells. Luciferase reporter assay showed that expression of FAM111B was directly regulated by miR-144-5p in LUAD cells. FAM111B knockdown assays showed that LUAD cells significantly suppressed malignant phenotypes, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. Furthermore, we investigated the FAM111B-mediated molecular networks in LUAD cells. Identifying target genes regulated by passenger strands of miRNAs may aid in the discovery of diagnostic markers and therapeutic targets for LUAD. [ABSTRACT FROM AUTHOR]

Strategies beyond hormone-related therapy need to be developed to improve prostate cancer mortality. Here, we show that FUBP1 and its methylation were essential for prostate cancer progression, and a competitive peptide interfering with FUBP1 methylation suppressed the development of prostate cancer. FUBP1 accelerated prostate cancer development in various preclinical models. PRMT5-mediated FUBP1 methylation, regulated by BRD4, was crucial for its oncogenic effect and correlated with earlier biochemical recurrence in our patient cohort. Suppressed prostate cancer progression was observed in various genetic mouse models expressing the FUBP1 mutant deficient in PRMT5-mediated methylation. A competitive peptide, which was delivered through nanocomplexes, disrupted the interaction of FUBP1 with PRMT5, blocked FUBP1 methylation, and inhibited prostate cancer development in various preclinical models. Overall, our findings suggest that targeting FUBP1 methylation provides a potential therapeutic strategy for prostate cancer management. [ABSTRACT FROM AUTHOR]