MyoD1 promotes the transcription of BIK and plays an apoptosis-promoting role in the development of gastric cancer.

Myogenic differentiation (MyoD) 1, which is known as a pivotal transcription factor during myogenesis, has been proven dysregulated in several cancers. However, litter is known about the precise role and downstream genes of MyoD1 in gastric cancer (GC) cells. Here, we report that MyoD1 is lowly expressed in primary GC tissues and cells. In our experiments, overexpression of MyoD1 inhibited cell proliferation. Downstream genes of MyoD1 regulation were investigated using RNA-Seq. As a result, 138 up-regulated genes and 20 down-regulated genes and 27 up-regulated lncRNAs and 20 down-regulated lncRNAs were identified in MyoD1 overexpressed MKN-45 cells, which participated in epithelial cell signaling in Helicobacter pylori infection, glycosaminoglycan biosynthesis (keratan sulfate), notch signaling pathway, and others. Among these genes, BIK was directly regulated by MyoD1 in GC cells and inhibited cancer cell proliferation. The BIK knockdown rescued the effects of MyoD1 overexpression on GC cells. In conclusion, MyoD1 inhibited cell proliferation via 158 genes and 47 lncRNAs downstream directly or indirectly that participated in multiple signaling pathways in GC, and among these, MyoD1 promotes BIK transcription by binding to its promoter, then promotes BIK-Bcl2-caspase 3 axis and regulates GC cell apoptosis.

Different fat-to-fiber ratios by changing wheat inclusion level impact energy metabolism and microbial structure of broilers.

Introduction: Dietary nutrient content is crucial for energy metabolism and development of gut microbiota. Herein, this study aimed to explore the effects of fat-to-fiber ratios on nutrient transporter, energy metabolism and gut microbiota when ingredients composition was altered. Methods: A total of 240 as-hatched broiler chickens were randomly assigned into three groups including low fat-high dietary fiber (LF-HD), medium fat-medium dietary fiber (MF-MD) and high fat-low dietary fiber (HF-LD), with diets being iso-protein, and broilers were offered the same commercial diets from 21 to 42 d. The data were analyzed using one-way ANOVA of SPSS. Results and Discussion: Results showed that HF-LD diet significantly increased glucose content and decreased triglyceride in serum of broilers (p < 0.05). The mRNA abundance of jejunal gene involved in glucose transporter and tricarboxylic acid (TCA) cycle was significantly increased in broilers fed with HF-LD diets. Compared with LF-HD, HF-LD had a lower abundance of Anaerofilum and CHKCI001, and an increased proportion of beneficial bacteria such as Alistipes, Catenibacillus, Intestinimonas, Lactobacillus, and Peptococcus (p < 0.05). Functional prediction of these microbial changes indicated that HF-LD diet drove caecal microbiota to participate in carbohydrate metabolism and TCA cycle (p < 0.05). Dietary HF-LD-induced microbiota changes were positively correlated with growth performance of broilers (p < 0.05). Therefore, HF-LD diet increased glucose transporters and energy metabolism in intestine and shaped microbial structure and metabolic pathways, which may benefit the growth performance of broilers.

Broiler Age Differently Affects Apparent Metabolizable Energy and Net Energy of Expanded Soybean Meal.

Accurately determining the energy values of ingredients is crucial for meeting energy requirements and achieving maximum production performance of animals. This study was conducted to measure the available energy values of three expanded soybean meals (ESBMs) for Arbor Acres male broilers from 14 to 16 day and 28 to 30 day using the difference method. A corn-soybean basal diet was formulated, and test diets were developed with 25% ESBMs as substitutes for energy-yielding ingredients. A completely randomized design was used for determining heat production and energy balance of broilers in 12 open-circuit respiration chambers, with six replicates per group. Prior to measurement, four (14 to 16 day) or two (28 to 30 day) birds per chamber were given a 4-day adaption to diets and chambers. The period lasted for 3 days to determine the apparent metabolizable energy (AME), nitrogen balance, gas exchanges, and heat production. Broilers fed test diets with 25% ESBM exhibited higher nitrogen intake (p < 0.05), nitrogen excreta (p < 0.05), and increased energy deposition as protein irrespective of age (p < 0.05). Furthermore, results showed that AME, nitrogen corrected AME (AMEn), and net energy (NE) values of 3 ESBMs averaged 10.48, 8.93, and 6.88 MJ/kg for broilers from 14 to 16 day, while averaged 11.91, 10.42, and 6.43 MJ/kg for broilers from 28 to 30 day. Broilers from 28 to 30 day showed significantly higher AMEn values but lower NE/AME values of ESBMs compared with those from 14 to 16 day (p < 0.05). Therefore, age-dependent energy values of a single ingredient should be considered in feed formulations to optimize economic returns.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio: Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events.

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor (ICI) and the occurrence of immune-related adverse events (irAEs). The predictive potential of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in determining ICI effectiveness has been extensively investigated, while limited research has been conducted on predicting irAEs. Furthermore, the combined model incorporating NLR and PLR, either with each other or in conjunction with additional markers such as carcinoembryonic antigen, exhibits superior predictive capabilities compared to individual markers alone. NLR and PLR are promising markers for clinical applications. Forthcoming models ought to incorporate established efficacious models and newly identified ones, thereby constituting a multifactor composite model. Furthermore, efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

Efficient gene delivery by multifunctional star poly (ß-amino ester)s into difficult-to-transfect macrophages for M1 polarization.

Gene delivery to macrophages holds great promise for cancer immunotherapy. However, traditional gene delivery methods exhibit low transfection efficiency in macrophages. The star-shaped topological structure of polymers is known to encapsulate genes inside their cores, thereby facilitating sustained release of the genetic material. Herein, combining the structural advantages of star polymers and the transfection advantages of poly (ß-amino ester)s (PAEs), we developed a novel linear oligomer grafting-onto strategy to synthesize a library of multi-terminal star structured PAEs (SPAEs), and evaluated their gene delivery efficiency in various tissue cells. The transfection with human hepatocellular carcinoma cells (HepG2, HCC-LM3 cells and MHCC-97H cells), rat normal liver cells (BRL-3 A cells), human ovarian cancer cells (A2780 cells), African green monkey kidney cells (Vero cells), human cervical cancer cells (HeLa cells), human chondrosarcoma cells (SW1353 cells), and difficult-to-transfect human epidermal keratinocytes (HaCaT cells) and normal human fibroblast cells (NHF cells) showed that SPAEs exhibited superior transfection profile. The GFP transfection efficiency of top-performing SPAEs in HeLa cells (96.1%) was 2.1-fold, and 3.2-fold higher compared to jetPEI and Lipo3000, respectively, indicating that the star-shaped topological structure can significantly enhance the transfection efficiency of PAEs. More importantly, the top-performing SPAEs could efficiently deliver Nod2 DNA to difficult-to-transfect RAW264.7 macrophages, with a high transfection efficiency of 33.9%, which could promote macrophage M1 polarization and enhanced CD8+ T cell response in co-incubation experiments. This work advances gene therapy by targeting difficult-to-transfect macrophages and remodeling the tumor immune microenvironment.

Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy. METHODS: Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy. RESULTS: Single-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7high macrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models. CONCLUSIONS: Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.

The Pyroptosis-Related Signature Composed of GSDMC Predicts Prognosis and Contributes to Growth and Metastasis of Hepatocellular Carcinoma.

BACKGROUND: Pyroptosis-related genes (PRG) are closely associated with the progression and metastasis of hepatocellular carcinoma (HCC). The predictive power of PRGs could be used to assess the clinical outcomes of HCC. METHODS: The Cancer Genome Atlas (TCGA) RNA-seq data and clinical information from patients with liver hepatocellular carcinoma (LIHC) were used to identify PRG with differentially expressed between HCC and normal samples. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox method, and multivariate Cox regression analysis were used to develop a prognostic model that included three PRGs. Gene set enrichment analysis (GSEA) was performed to identify differential immune cells and their associated pathways. The expression of Gasdermin C (GSDMC) in the HCC samples was detected by western blotting, and the function of GSDMC in HCC proliferation and metastasis was detected by the Cell Counting Kit-8 (CCK-8), colony formation, cell invasion, and wound healing assays. RESULTS: Of 52 PRGs, GSDMC, Bcl-2 homologusantagonist/ killer 1 (BAK1), and NOD-like receptor thermal protein domain associated protein 6 (NLRP6) were selected to establish a prognostic model. The model successfully differentiated HCC patients with varied survival in the TCGA training and test cohorts, as well as the International Cancer Genome Consortium (ICGC) validation cohorts. The risk score was proven to be an independent prognostic factor. In addition, we also reported a marked upregulation of GSDMC in HCC tissues, which could be induced by CD274 (PD-L1). Overexpression of GSDMC contributes to HCC cells invasion, proliferation, and migration. CONCLUSIONS: The three PRGs signatures containing GSDMC independently predicted HCC prognosis. As a new driver molecule, GSDMC could play a tumor-promoting role by facilitating HCC growth and metastasis.

CD36-BATF2\MYB Axis Predicts Anti-PD-1 Immunotherapy Response in Gastric Cancer.

Despite the utilization of anti-PD-1 therapy in gastric cancer (GC), the absence of a reliable predictive biomarker continues to pose a challenge. In this study, we utilized bioinformatic analysis and immunohistochemistry to develop a prediction model for activated CD4+ memory T cells, considering both mRNA and protein levels. An elevation of activated CD4+ memory T cells in GC was noted, which exhibited a strong association with the patients' overall survival. By utilizing WGCNA and DEG analysis, we discovered that BATF2, MYB, and CD36 are genes that exhibit differential expression and are linked to activated CD4+ memory T cells. Afterwards, a forecast model was built utilizing Stepwise regression and immunohistochemistry relying on the three genes. The model's high-risk score showed significant associations with a suppressive immune microenvironment. Moreover, our model exhibited encouraging prognostic value and superior performance in predicting response to immune checkpoint blockade therapy compared with the conventional CD8+PD-L1 model. In terms of mechanism, CD36 could function as a receptor upstream that identifies Helicobacter pylori and fatty acids. This recognition then results in the reduction of the BATF2-MYB protein complex and subsequent alterations in the transcription of genes associated with classical T cell activation. As a result, the activation state of CD4+ memory T cells is ultimately suppressed. The CD36-BATF2/MYB signature serves as a robust predictor of anti-PD-1 immunotherapy response in GC.

RNF6 promotes gastric cancer progression by regulating CCNA1/CREBBP transcription.

Ring finger protein 6 (RNF6) is a member of the E3 ubiquitin ligase family. Previous studies have reported the involvement of RNF6 as a ubiquitin ligase in the progression of gastric cancer (GC). However, this study found that RNF6 has a clear localization in the nucleus of GC, indicating a role other than ubiquitin ligase. Further chromatin immunoprecipitation sequencing (ChIP-seq) analysis revealed that RNF6 has DNA binding and transcriptional regulatory effects and is involved in important pathways such as tumor cell cycle and apoptosis. Cyclin A1 (CCNA1) and CREB binding protein (CREBBP) are downstream targets for RNF6 transcription regulation in GC. RNF6 binds to the promoter region of CCNA1/CREBBP and is actively regulating their expression in GC cells. Silencing CCNA1/CREBBP partially reversed the promoting effect of RNF6 overexpression on the biological function of GC cells. Our study suggests that RNF6 promotes the progression of GC by regulating CCNA1/CREBBP transcription.

The ionome and proteome landscape of aging in laying hens and relation to egg white quality.

The ionome is essential for maintaining body function and health status by participating in diverse key biological processes. Nevertheless, the distribution and utilization of ionome among different organs and how aging impacts the ionome leading to a decline in egg white quality remain unknown. Thus, we used inductively coupled plasma mass spectrometry (ICP-MS) to analyze 35 elements and their isotopic contents in eight organs of laying hens at 35, 72, and 100 weeks. Moreover, the magnum proteome, amino acids in egg white, and egg white quality were analyzed in laying hens at three different ages using 4D proteomics techniques, an amino acid analyzer, and an egg quality analyzer. Across the organs, we identified varying distribution patterns among macroelements (Mg24, Ca43/44, K39, and P31), transition metals (Zn64/66, Cu63/65, Fe56/57, and Mn55), and toxic elements (Pb208, Ba137, and Sr86). We observed an organ-specific aging pattern characterized by the accumulation of toxic elements (Pb208, Ba137, and Sr86) and calcification in the small intestine. Additionally, a decrease in the utilization of essential trace elements selenium (Se78/82) and manganese (Mn55) was noted in the oviduct. By analyzing ionome in tandem with egg quality, egg white amino acids, and proteome, we unveiled that the reduction of selenium and manganese concentrations in the magnum during the aging process affected amino acid metabolism, particularly tryptophan metabolism, thereby inhibiting the amino acid synthesis in the magnum. Furthermore, it accelerated the senescence of magnum cells through necroptosis activation, leading to a decline in the albumen secretion function of the magnum and subsequently reducing egg white quality. Overall, this study provides insights into the evolution of 35 elements and their isotopes across 8 organs of laying hens with age. It also reveals the elemental composition, interactions, and utilization patterns of these organs, as well as their correlation with egg white quality. The present study highlights the significance of ionome and offers a comprehensive perspective on the selection of ionome for regulating the aging of laying hens.

IGF2BP3-EGFR-AKT axis promotes breast cancer MDA-MB-231 cell growth.

Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an emerging prognostic indicator, and its elevated expression correlates with malignancy in a broad spectrum of cancers. However, its regulatory networks have not yet been reported. In this study, we identified the regulatory targets of IGF2BP3 in breast cancer MDA-MB-231 cells using RNA immunoprecipitation sequencing (RIP-seq) and high-throughput RNA-sequencing (RNA-seq). We discovered that these targets were enriched in the inflammatory response, endoplasmic reticulum stress, cell cycle, and cancer-related pathways, providing a new perspective for better understanding the functional mechanisms of IGF2BP3. Moreover, we identified that the epidermal growth factor receptor (EGFR), a downstream target, is regulated by IGF2BP3. IGF2BP3 binds to and protects EGFR mRNA from degradation and facilitates cell proliferation via the EGFR/AKT pathway in MDA-MB-231 cells. In addition, IGF2BP3 expression was robust and could not be altered by stimulation with EGF and anti-EGFR siRNA or EGFR signaling pathway inhibitors (gefitinib, LY294002 and SL-327). These results demonstrate that IGF2BP3, as a stubborn oncogene, promotes triple-negative breast cancer MDA-MB-231 cell proliferation by strengthening the role of the EGFR-AKT axis.

Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.

MAD2L1 is transcriptionally regulated by TEAD4 and promotes cell proliferation and migration in colorectal cancer.

The molecular mechanism of network regulation in the occurrence and development of colorectal cancer (CRC) has been constantly improved. Here, we investigated the biological effects of TEAD4-MAD2L1 axis on proliferation and metastasis of human CRC cells. This study revealed that the expressions of MAD2L1 and TEAD4 in CRC tissues and CRC cell lines were significantly higher than those in adjacent epithelial tissues and normal intestinal epithelial cell line NCM460, and their expressions were significantly positively correlated; Moreover, inhibiting the expression of MAD2L1 or TEAD4 can inhibit the proliferation and migration of CRC cells and promote apoptosis. In addition, the promoter region of MAD2L1 gene has a TEAD4 binding site (motif sequence), and the transcription of MAD2L1 is positively regulated by TEAD4 protein; The inhibition of promotion/migration and promotion of apoptosis of CRC cells by silencing TEAD4 can be saved by the high expression of MAD2L1. In conclusion, our study suggests that the transcription and expression of MAD2L1 is regulated by TEAD4, which further promotes the proliferation and migration of CRC cells in vitro and in vivo, and inhibits apoptosis. MAD2L1 and TEAD4 are potential biomarkers for colorectal cancer.

Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan.

Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains to be elucidated. Here, wild-type aging mice and Zmpste24-/- progeroid mice were used to investigate the role of genistein in lifespan and homeostasis of the aging gut in mammals. A series of longitudinal, clinically relevant measurements were performed to evaluate the effect of genistein on healthspan. It was found that dietary genistein promoted a healthier and longer life and was associated with a decrease in the levels of systemic inflammatory cytokines in aging mice. Furthermore, dietary genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. A distinct genistein-mediated alteration in gut microbiota was observed by increasing Lachnospira abundance and short-chain fatty acid (SCFA) production. Further fecal microbiota transplantation and dirty cage sharing experiments indicated that the gut microbiota from genistein-fed mice rejuvenated the aging gut and extended the lifespan of progeroid mice. It was demonstrated that genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced intestinal organoid damage. Moreover, genistein-associated propionate promoted regulatory T cell-derived interleukin 10 production, which alleviated macrophage-derived inflammation. This study provided the first data, to the authors' knowledge, indicating that dietary genistein modulates homeostasis in the aging gut and extends the healthspan and lifespan of aging mammals. Moreover, the existence of a link between genistein and the gut microbiota provides a rationale for dietary interventions against age-associated frailty.

Comparative study of apparent metabolizable energy and net energy values of dephenolized cottonseed proteins for laying hens.

Optimizing the energy utilization of nutrients and ensuring maximum benefits are continuous goals for livestock producers. The net energy (NE) value of feed reflects its nutritional value in the precision feeding system. An experiment was conducted to determine the apparent metabolizable energy (AME) and NE values of 3 types of dephenolized cottonseed protein (DCP) for Hy Line Brown hens aged 42 to 45 weeks using the reference diet substitution method. A reference diet based on corn soybean meal was used to meet the nutritional needs of Hy Line Brown laying hens. To render the crude protein and energy values of the 3 test diets similar, 10.5%, 12%, and 16% of the gross energy yielding ingredients from the reference diet were replaced with DCP 1, DCP 2, and DCP 3, respectively. The birds were fed 4 diets during a 7-d adaptation period. After the dietary adaptation period, 2 birds per replicate from each treatment group were placed in an individual open circuit respiratory calorimetry chamber for a 3-d experimental period. Daily O2 consumption and CO2 production were recorded, and excreta samples were collected. The AME values of DCP 1, DCP 2, and DCP 3 were 3,049.05, 2,820.13, and 2,982.31 kcal/kg of dry matter (DM), respectively. The NE values of DCP 1, DCP 2, DCP 3 were 1,475.77, 1,910.31, and 1,905.37 kcal/kg of DM, respectively, and the NE:AME ratios were 48.40%, 67.74%, and 63.89%, respectively. Our data show that the AME value of DCP does not reflect the nutritional value of the feed. The NE value of DCP with a high ME value was not necessarily high.

MECP2 promotes the migration and invasion of gastric cancer cells by modulating the Notch1/c-Myc/mTOR signaling pathways by suppressing FBXW7 transcription.

Methyl-CpG-binding protein 2 (MECP2), an epigenetic regulatory factor, promotes the carcinogenesis and progression of a number of cancers. However, its role in the migration and invasion of gastric cancer (GC), as well as the underlying molecular mechanisms, remain unclear. In this study, we found that MECP2 promoted the migration, invasion and metastasis of GC cells. Investigation of the molecular mechanism revealed that MECP2 repressed F-box and WD40 domain protein 7 (FBXW7) transcription in GC by binding to the methylated CpG sites in the FBXW7 promoter region. MECP2 expression was markedly negatively correlated with the FBXW7 level in GC tissues. FBXW7 expression was significantly downregulated in GC tissues and cell lines, and low FBXW7 expression was correlated with unfavorable clinicopathologic features. FBXW7 inhibited cell migration and invasion by regulating the Notch1/c-Myc/mTOR signaling pathways, and knockdown of FBXW7 reversed the effects of silencing MECP2. Moreover, MECP2 upregulated the Notch1/c-Myc/mTOR signaling pathways by inhibiting FBXW7 expression at the transcriptional level. This study demonstrates that MECP2 promotes the migration and invasion of GC cells by modulating the Notch1/c-Myc/mTOR signaling pathways via suppression of FBXW7 transcription. These findings suggest that MECP2 may be a novel effective therapeutic target in GC.

Identification of prognostic miRNA-mRNA regulatory network in the progression of HCV-associated cirrhosis to hepatocellular carcinoma.

Background: Long-term hepatitis C virus (HCV) infection is strongly associated with hepatocellular carcinoma (HCC), yet the mechanisms of the progression process remain unclear. The research is aiming to establish a crucial prognostic model that indicates the risk of HCV-associated cirrhosis evolving into HCC. Methods: Differentially expressed microRNAs (DE-miRNAs) and differentially expressed genes (DEGs) between HCV-associated cirrhosis and HCC were screened from the GSE40744 and GSE6764 datasets, respectively. Downstream target genes of DE-miRNAs were predicted by the miRNet tool and then overlapped with the DEGs to select intersection genes. The GSE15654 was downloaded to establish a prognostic model. Expression levels of risk genes and their corresponding miRNAs were measured in liver tissues of clinical patients. HCC cell lines with UHRF1 knockdown or overexpression were assayed for cell proliferation and migration. Results: Thirty-nine DE-miRNAs and 796 DEGs are identified between HCV-associated cirrhosis and HCC. Main intersection genes and their corresponding miRNAs constitute a miRNA-mRNA regulatory network. PABPC1 (Polyadenylate-binding protein 1), SLC2A9 (solute carrier gene family 2, member 9), and UHRF1 (ubiquitin-like with PHD and ring finger domains 1) form a prognostic model indicating the risk of HCC development among HCV-associated cirrhosis. The genetic mutations of PABPC1, SLC2A9, and UHRF1 in HCC patients are 9%, 0.8%, and 0.6%, respectively. Compared to that in HCV-associated cirrhosis, the expression levels of PABPC1 and UHRF1 are higher while the expression level of SLC2A9 is lower in clinical HCV-associated HCC samples. UHRF1 enhances the proliferation and migration ability of HCC cells. Conclusions: PABPC1, SLC2A9, and UHRF1 and their corresponding miRNAs are involved in the evolution process of HCV-associated cirrhosis into malignant HCC. UHRF1 serves as an oncogene that promotes the proliferation and migration of HCC cells.

Significance of HOXD transcription factors family in progression, migration and angiogenesis of cancer.

The transcription factors (TFs) of the HOX family play significant roles during early embryonic development and cellular processes. They also play a key role in tumorigenesis as tumor oncogenes or suppressors. Furthermore, TFs of the HOXD geFIne cluster affect proliferation, migration, and invasion of tumors. Consequently, dysregulated activity of HOXD TFs has been linked to clinicopathological characteristics of cancer. HOXD TFs are regulated by non-coding RNAs and methylation of DNA on promoter and enhancer regions. In addition, HOXD genes modulate the biological function of cancer cells via the MEK and AKT signaling pathways, thus, making HOXD TFs, a suitable molecular marker for cancer prognosis and therapy. In this review, we summarized the roles of HOXD TFs in different cancers and highlighted its potential as a diagnostic and therapeutic target.

Future therapies for pancreatic carcinoma: Insights into cancer precision medicine.

Pancreatic carcinoma (PC) has one of the highest rates of cancer-related death worldwide. Except for surgery, adjuvant chemotherapy, chemoradiotherapy, and immunotherapy have shown various efficacies depending on the stage of the patient. We read the review "Current and emerging therapeutic strategies in pancreatic cancer: Challenges and opportunities" and offer some opinions that may improve its precision and completeness. This review presents a map of appropriate therapies for PC at different stages. Based on the clinical trial outcomes mentioned in the review, we evaluated the potential therapeutic options for PC and helped explain the contradictory efficacy between different programmed cell death protein 1/programmed cell death ligand 1 clinical trials, which may have resulted from the unique features of PC. Although R0 resection and adjuvant chemotherapy are still the gold standards for PC, new modalities, with or without clinical validation, are needed to establish more specific and precise treatments for PC.