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Background and purpose: Pancreatic cancer is a highly malignant disease. Most patients are in advanced stage upon diagnosis. Systemic chemotherapy is an important treatment method, but the chemotherapy drug resistance to tumors brings many problems to clinical treatment. As a commonly used chemotherapy drug, paclitaxel can induce apoptosis in tumor cells. The FBW7 gene is a tumor suppressor gene, and the loss of its function can lead to tumor occurrence and progression. Research has shown that it has the effect of promoting tumor cell apoptosis and inhibiting tumor proliferation. In addition, this gene has been proven to promote apoptosis and ferroptosis, which increase the effect of chemotherapy drugs. Pyroptosis is a programmed cell death mode mediated by gasdermin (GSDM) protein, and this cell death is often accompanied by inflammatory reactions. This study aimed to investigate whether FBW7 gene can promote the anti-tumor effect of paclitaxel by increasing pyroptosis. Methods: A PANC-1 cell line overexpressing FBW7 was constructed using lentivirus transfection. The correlation between FBW7 and GSDME gene expressions was detected by immunohistochemistry in clinical samples, and the expression levels of mRNA and protein were detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. We observed the morphological changes of cells treated with paclitaxel under light microscopy. Cell counting kit-8 (CCK-8) was used to detect the effect of paclitaxel on cell viability, and flow cytometry and lactate dehydrogenase (LDH) release assay were performed to detect the effect of paclitaxel on cell death. Western blot was used to detect caspase-3 and GSDME activation after paclitaxel treatment. Results: RTFQ-PCR and Western blot experiments showed that overexpression of FBW7 gene increased the expression of GSDME. Immunohistochemical staining of pathological sections of clinical patients also showed that the expressions of FBW7 and GSDME genes was positively correlated in vivo. Flow cytometry and LDH release experiments showed that the level of cell death in pancreatic cancer cell line PANC-1 overexpressing FBW7 was significantly increased compared with its empty vector (EV) cells after being treated with paclitaxel. Under light microscopy, it was observed that the number of cells with pyroptosis was significantly higher in PANC-1 cell lines overexpressing FBW7 than in EV cells. The CCK-8 experiment results showed that the cell viability was significantly lower in FBW7 overexpressed cell lines than in EV cells after paclitaxel treatment. Western blot experiment results showed that after pancreatic cancer cell line PANC-1 was treated with paclitaxel, the protein expressions of active-caspase-3 and GSDME-NT in FBW7 overexpression cell lines increased, which proved that they had more obvious activation, indicating that the FBW7 gene can increase the sensitivity of PANC-1 cells to paclitaxel through caspase-3/GSDME signaling pathway induced cell pyroptosis. Conclusion: FBW7 can increase the sensitivity of pancreatic cancer cells to paclitaxel by increasing the expression of GSDME, which is realized through caspase-3/GSDME pathway.

Since the prognosis of patients with pancreatic cancer is very poor and there is a lack of treatment methods, this study is performed to investigate the function of PITX2 in pancreatic stellate cells (PSCs) in the progression of pancreatic cancer. Scientific hypotheses are proposed according to bioinformatics analysis and tissue microarray analysis. Stable knockdown of PITX2 in PSCs is achieved through lentiviral infection. The relative expressions of PITX2, α-SMA, vimentin, CTNNB1, AXIN1 and LEF1 are measured in wild-type PSCs and PITX2-knockdown PSCs. Proliferative capacity is measured by EdU assay. After coculture with PSCs, the proliferation, invasion and migration capacity of pancreatic cancer cells are tested. EMT and Wnt/β-catenin downstream genes of pancreatic cancer cells are investigated to reveal the potential mechanism. Bioinformatics analysis reveals that the PITX2 gene is highly expressed in stromal cells in pancreatic cancer and is correlated with squamous-type PDAC. Analysis of PDAC tissue microarray further demonstrates that high PITX2 level in stromal cells is correlated with poor prognosis in PDAC. After stable knockdown of PITX2 in PSCs, the relative protein levels of α-SMA, vimentin, CTNNB1, AXIN1 and LEF1 are decreased, and the proliferative capacity of PSCs is also decreased. After coculture with PSCs, in which PITX2 expression is downregulated, the proliferation, invasion and migration capacities of pancreatic cancer cells are inhibited. Thus, our results show that PITX2-silenced PSCs inhibit the growth, migration and invasion of pancreatic cancer cells via reduced EMT and Wnt/β-catenin signaling.

Background: There is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC). Methods: The clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed. Results: The analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival. Conclusions: LPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival. [ABSTRACT FROM AUTHOR]

Background: Nuclear receptor coactivator 6 (NCoA6) is overexpressed in various cancers and considered a multifunctional coactivator of various transcription factors and nuclear receptors. However, the role of NCoA6 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. Methods: NCoA6 expression data in PDAC were extracted from TCGA and GTEx databases, and their correlation with survival outcomes were analyzed using the Kaplan–Meier plotter database. NCoA6 protein expression in PDAC tissues was evaluated using immunohistochemistry. RNA‐sequencing technology was used to sequence the transcriptome of NCoA6‐silenced PANC‐1 cells, followed by differential expression, GO/KEGG and GSEA analyses. The effects of NCoA6 on cell proliferation, migration, invasion, cell cycle, and apoptosis were determined in two representative cell lines (PANC‐1 and SW1990). Western blotting, qPCR, and co‐immunoprecipitation were performed to explore the mechanism of action of NCoA6 in PDAC cells. Results: NCoA6 expression was markedly increased in PDAC tissues, and high NCoA6 expression was associated with poor survival prognosis. However, there was no significant relationship between NCoA6 expression and metastasis in PDAC patients. Our RNA‐sequencing data analysis found 1194 significant differentially expressed genes between the control and NCoA6‐silenced PANC‐1 cells. GO/KEGG analysis results mainly focused on cytokine production, cytokine activity, and cytokine‐cytokine receptor interactions. GSEA results showed that the knockdown of NCoA6 affected the expression of histone deacetylase 1 (HDAC1) targeted genes. NCoA6 knockdown suppressed proliferation, migration, and invasion of PDAC cells. Finally, western blotting, qPCR, and co‐immunoprecipitation results showed that NCoA6 interacted with HDAC1 and that NCoA6 expression was negatively correlated with F‐box and WD repeat domain‐containing 7 (FBW7) and caudal‐related homeobox transcription factor 2 (CDX2) expression in pancreatic cancer. Conclusions: NCoA6 has a profound effect on cell proliferation, migration, invasion, and prognosis of PDAC and is potentially related to the expression of HDAC1, FBW7, and CDX2. Our results may provide novel therapeutic strategies for PDAC patients. [ABSTRACT FROM AUTHOR]

Background: As an oncogene, SETD8 can promote tumour growth and tumour cell proliferation. This study aims to reveal the relationship between SETD8 and ferroptosis in pancreatic cancer and its role in pancreatic cancer to provide a possible new direction for the comprehensive treatment of pancreatic cancer. Methods: The downstream targets were screened by RNA sequencing analysis. Western blot, Real-time Quantitative PCR (qPCR) and immunohistochemistry showed the relationship between genes. Cell proliferation analysis and cell metabolite analysis revealed the function of genes. Chromatin immunoprecipitation (CHIP) assays were used to study the molecular mechanism. Results: The potential downstream target of SETD8, RRAD, was screened by RNA sequencing analysis. A negative correlation between SETD8 and RRAD was found by protein imprinting, Real-time Quantitative PCR (qPCR) and immunohistochemistry. Through cell proliferation analysis and cell metabolite analysis, it was found that RRAD can not only inhibit the proliferation of cancer cells but also improve the level of lipid peroxidation of cancer cells. At the same time, chromatin immunoprecipitation analysis (CHIP) was used to explore the molecular mechanism by which SETD8 regulates RRAD expression. SETD8 inhibited RRAD expression. Conclusions: SETD8 interacts with the promoter region of RRAD, which epigenetically silences the expression of RRAD to reduce the level of lipid peroxidation in pancreatic cancer cells, thereby inhibiting ferroptosis in pancreatic cancer cells and resulting in poor prognosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objective. To develop a multimodal model that combines multiphase contrast-enhanced computed tomography (CECT) imaging and clinical characteristics, including experts’ experience, to preoperatively predict lymph node metastasis (LNM) in pancreatic cancer patients. Methods. We proposed a new classifier fusion strategy (CFS) based on a new evidential reasoning (ER) rule (CFS-nER) by combining nomogram weights into a previous ER rule-based CFS. Three kernelled support tensor machine-based classifiers with plain, arterial, and venous phases of CECT as the inputs, respectively, were constructed. They were then fused based on the CFS-nER to construct a fusion model of multiphase CECT. The clinical characteristics were analyzed by univariate and multivariable logistic regression to screen risk factors, which were used to construct correspondent risk factor-based classifiers. Finally, the fusion model of the three phases of CECT and each risk factor-based classifier were fused further to construct the multimodal model based on our CFS-nER, named MMM-nER. This study consisted of 186 patients diagnosed with pancreatic cancer from four clinical centers in China, 88 (47.31%) of whom had LNM. Results. The fusion model of the three phases of CECT performed better overall than single and two-phase fusion models; this implies that the three considered phases of CECT were supplementary and complemented one another. The MMM-nER further improved the predictive performance, which implies that our MMM-nER can complement the supplementary information between CECT and clinical characteristics. The MMM-nER had better predictive performance than based on previous classifier fusion strategies, which presents the advantage of our CFS-nER. Conclusion. We proposed a new CFS-nER, based on which the fusion model of the three phases of CECT and MMM-nER were constructed and performed better than all compared methods. MMM-nER achieved an encouraging performance, implying that it can assist clinicians in noninvasively and preoperatively evaluating the lymph node status of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Although some factors that predict the prognosis in pancreatic neuroendocrine tumor (pNET) have been confirmed, the predictive value of lymph node metastasis (LNM) in the prognosis of pNETs remains conflicting and it is not clear whether regional lymphadenectomy should be performed in all grades of tumors.Methods: We included pNET patients undergoing surgery in Shanghai pancreatic cancer institute (SHPCI). The risk factors for survival were investigated by the Kaplan-Meier method and Cox regression model. We evaluated the predictors of LNM using Logistic regression.Results: For 206 patients in the SHPCI series, LNM was an independent prognostic factor for entire cohort suggested by multivariate Cox regression analysis. LNM (P = 0.002) predicted poorer overall survival (OS) in grade 2/3 cohort, but there is no significant association between LNM and OS in grade 1 cohort. Grade (P < 0.001) and size (P = 0.049) predicted LNM in entire cohort. Grade (P = 0.002) predicted LNM while regardless of size in grade 2/3 cohort.Conclusions: Based on our own retrospective data obtained from a single center series, LNM seems to be associated with poorer outcome for patients with grade 2/3 and/or grade 1 > 4 cm tumors. On the other way, LNM was seems to be not associated with prognosis in patients with grade 1 tumors less than 4 cm. Moreover, tumor grade and tumor size seem to act as independent predictors of LNM. Thus, regional lymphadenectomy should be performed in grade 2/3 patients but was not mandatory in grade 1 tumors < 4 cm. It is reasonable to perform functional sparing surgery for grade 1 patients or propose a clinical-radiological monitoring. [ABSTRACT FROM AUTHOR]

Background: The neddylation pathway is aberrantly overactivated in multiple human cancers and has been indicated as an effective target for anticancer therapy in clinical trials. We aimed to study whether the neddylation pathway is upregulated in pancreatic cancer and whether pevonedistat, a first-in-class anticancer agent specifically targeting this pathway, will suppress cancer tumorigenesis and progression. Methods: We evaluated the expression pattern of neddylation pathway components in 179 pancreatic adenocarcinoma (PAAD) compared with 171 normal tissues from The Cancer Genome Atlas (TCGA) dataset and further assessed PAAD patient prognosis with high neddylation pathway expression via Gene Expression Profiling Interactive Analysis (GEPIA). We then analyzed malignant cancer phenotypes both in vitro and in vivo , as well as intrinsic molecular mechanisms upon pevonedistat treatment. Results: We found that the neddylation pathway was hyperactivated in pancreatic cancer. Patients with high neddylation pathway expression exhibited worse prognoses. Pevonedistat significantly inhibited the cancer cell cycle, cell growth, and proliferation; increased cell apoptosis; and decreased cancer cell xenografts in a mouse model. Mechanistically, pevonedistat treatment and the siRNA knockdown neddylation pathway were able to remarkably induce the accumulation of Wee1, p27, and p21. Further mechanistic studies revealed that pevonedistat mainly impaired the ubiquitination level and delayed the protein degradation of Wee1, p27, and p21. Conclusions: Our results showed that pevonedistat targeted the overexpression of the neddylation pathway in pancreatic cancer to induce cell growth suppression by inducing the accumulation of the cell cycle regulators Wee1, p27, and p21, which provides sound evidence for the clinical trial of pevonedistat for pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

The baseline is referring to the patient before therapy administration gl Interesting, VEGF promotes gemcitabine resistance in pancreatic cancer cells (Figures 2A and 2B). Finally, we silenced c-Myc in VEGF-stimulated MIA PaCa-2 and SW1990 cells, and found that c-Myc suppression or knockdown could reverse the effects of VEGF on the IC50 values of gemcitabine of pancreatic cancer cells (Figures S2E and S2F). The baseline is referring to the patient before therapy administration. gl GLO:F2H7/01aug21:ctm2398-sup-0002-FigureS2.jpg PHOTO (COLOR): Figure S2 Silencing c-Myc reverses the effect of VEGF on RRM1. Dear Editor, The regimen of nab-paclitaxel and gemcitabine (AG) has been widely used as the first-line chemotherapy for advanced pancreatic cancer; the prolonged survival time is still less than 2 months.1 Kim et al demonstrated that paclitaxel can induce vascular endothelial growth factor-A (VEGF) expression which could facilitate the survival of neoplastic and tumor cells, thus protecting both endothelial and stroma cells from cytotoxic death while promoting angiogenesis.2-4 To explore the neovascularization in patients with pancreatic ductal adenocarcinoma (PDAC) treated with AG or gemcitabine alone, we first examined the I K SP trans sp i value in the tumor by Dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). [Extracted from the article]

Objectives: Accumulated evidence suggests that Pin1 contributes to oncogenesis of diverse cancers. However, the underlying mechanism of oncogenic function of Pin1 in PDAC requires further exploration. Materials and Methods: IHC was performed using PDAC tissues. Western blot, PCR, immunofluorescence and transwell were performed using cell lines. GSEA were applied for possible downstream pathways. ChIP assay and dual luciferase were used for assessment of transcriptional activity. Results: Both Pin1 and IL‐18 levels are increased in primary PDAC tissues and that their levels are positively correlated. High expression of IL‐18 is a predictor of poor prognoses. Pin1 promoted pancreatic cancer cell proliferation and motility by increasing IL‐18 expression, while Pin1 knockdown also inhibited the tumour‐promoting effect of IL‐18. Both Pin1 and IL‐18 could enhance the NFκB activity in pancreatic cancer cells. When bound to the p65 protein, Pin1 promoted p65 phosphorylation and its nuclear translocation. In the nucleus, Pin1 and p65 simultaneously bound to the IL‐18 promoter and enhanced IL‐18 transcription. In addition, recruitment of p65 to the IL‐18 promoter was decreased in Pin1‐silenced cells. Conclusions: Our study improves the understanding of Pin1 in tumour‐promoting inflammation in PDAC, which is a hallmark of cancer; Pin1 interacted with p65 in PDAC and enhanced NF‐κB signalling and downstream transcriptional activation of IL‐18, with increased IL‐18 continuously activating NF‐κB signalling, which then forms a positive feedback loop. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the roles of the homeodomain‐interacting protein kinase (HIPK) family of proteins in pancreatic cancer prognosis and the possible molecular mechanism. Materials and Methods: The expression of HIPK family genes and their roles in pancreatic cancer prognosis were analysed by using The Cancer Genome Atlas (TCGA). The roles of HIPK2 in pancreatic cancer proliferation and glycolysis were tested by overexpression of HIPK2 in pancreatic cancer cells, followed by cell proliferation assay, glucose uptake analysis and Seahorse extracellular flux analysis. The mechanism of action of HIPK2 in pancreatic cancer proliferation and glycolysis was explored by examining its effect on the ERK/cMyc axis. Results: Decreased HIPK2 expression indicated worse prognosis of pancreatic cancer. Overexpression of HIPK2 in pancreatic cancer cells decreased cell proliferation and attenuated aerobic glycolysis, which sustained proliferation of cancer cells. HIPK2 decreased cMyc protein levels and expression of cMyc‐targeted glycolytic genes. cMyc was a mediator that regulated HIPK2‐induced decrease in aerobic glycolysis. HIPK2 regulated cMyc protein stability via ERK activation, which phosphorylated and controlled cMyc protein stability. Conclusions: HIPK2 suppressed proliferation of pancreatic cancer in part through inhibiting the ERK/cMyc axis and related aerobic glycolysis. [ABSTRACT FROM AUTHOR]

Pancreatic cancer cells have a much higher metabolic demand than that of normal cells. However, the abundant interstitium and lack of blood supply determine the lack of nutrients in the tumour microenvironment. Although pancreatic cancer has been reported to supply extra metabolic demand for proliferation through autophagy and other means, the specific regulatory mechanisms have not yet been elucidated. In this study, we focused on transcription factor EB (TFEB), a key factor in the regulation of autophagy, to explore its effect on the phenotype and role in the unique amino acid utilisation pattern of pancreatic cancer cells (PCCs). The results showed that TFEB, which is generally highly expressed in pancreatic cancer, promoted the proliferation and metastasis of PCCs. TFEB knockdown inhibited the proliferation and metastasis of PCCs by blocking the catabolism of branched‐chain amino acids (BCAAs). Concerning the mechanism, we found that TFEB regulates the catabolism of BCAAs by regulating BCAT1, a key enzyme in BCAA metabolism. BCAA deprivation alone did not effectively inhibit PCC proliferation. However, BCAA deprivation combined with eltrombopag, a drug targeting TFEB, can play a two‐pronged role in exogenous supply deprivation and endogenous utilisation blockade to inhibit the proliferation of pancreatic cancer to the greatest extent, providing a new therapeutic direction, such as targeted metabolic reprogramming of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Ferroptosis inhibits tumor progression in pancreatic cancer cells, while PITX2 is known to function as a pro-oncogenic factor in various tumor types, protecting them from ferroptosis and thereby promoting tumor progression. In this study, we sought to investigate the regulatory role of PITX2 in tumor cell ferroptosis within the context of pancreatic cancer. We conducted PITX2 knockdown experiments using lentiviral infection in two pancreatic cancer cell lines, namely PANC-1 and BxPC-3. We assessed protein expression through immunoblotting and mRNA expression through RT-PCR. To confirm PITX2 as a transcription factor for GPX4, we employed Chromatin Immunoprecipitation (ChIP) and Dual-luciferase assays. Furthermore, we used flow cytometry to measure reactive oxygen species (ROS), lipid peroxidation, and apoptosis and employed confocal microscopy to assess mitochondrial membrane potential. Additionally, electron microscopy was used to observe mitochondrial structural changes and evaluate PITX2's regulation of ferroptosis in pancreatic cancer cells. Our findings demonstrated that PITX2, functioning as a transcription factor for GPX4, promoted GPX4 expression, thereby exerting an inhibitory effect on ferroptosis in pancreatic cancer cells and consequently promoting tumor progression. Moreover, PITX2 enhanced the invasive and migratory capabilities of pancreatic cancer cells by activating the WNT signaling pathway. Knockdown of PITX2 increased ferroptosis and inhibited the proliferation of PANC-1 and BxPC-3 cells. Notably, the inhibitory effect on ferroptosis resulting from PITX2 overexpression in these cells could be countered using RSL3, an inhibitor of GPX4. Overall, our study established PITX2 as a transcriptional regulator of GPX4 that could promote tumor progression in pancreatic cancer by reducing ferroptosis. These findings suggest that PITX2 may serve as a potential therapeutic target for combating ferroptosis in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Constitutive ERK1/2 activation has been frequently observed in pancreatic adenocarcinoma (PDAC). How ERK1/2 activation status been potentiated and maintained by epigenetic mechanisms has seldom been discussed in PDAC. In this study, we first examined the expression status of p-ERK1/2 in PDAC tissues by immunohistochemical staining and then screened possible epigenetic factors that displayed different expression status between p-ERK1/2 high and low groups by RNA profiling, and found that SETD8 displayed an increased expressional pattern in p-ERK1/2high patient group. Then the impact of SETD8 on the proliferation of PDAC cells were investigated on the basis of gain or loss-of-function assays. RNA sequencing assays were performed to screen potential SETD8 downstream targets that contribute to ERK1/2 activation. Mass spectrometry and transcriptional analysis, including dual-luciferase assay and chromatin immunoprecipitation assay (ChIP), were used to explore the molecular mechanisms that governing SETD8-mediated ERK1/2 activation. In vitro cell line studies and in vivo xenograft mouse model studies indicated that SETD8 promoted cell proliferation and increased tumor formation capacity of PDAC cell lines. Mechanism explorations uncovered that SETD8 suppressed the expression of DUSP10, which was responsible for dephosphorylation of ERK1/2. Mass spectrometry and transcriptional analysis results demonstrated that STAT3 interacted with SETD8 and recruited SETD8 to the promoter region of DUSP10, leading to epigenetic silencing of DUSP10 and the resultant activation of ERK1/2. In conclusion, SETD8 interacts with STAT3 on DUSP10 promoter region and epigenetically silences DUSP10 expression. Decreased DUSP10 expression in PDAC potentiates activation of ERK1/2 phosphorylation, resulting in unfavorable prognosis of PDAC. [ABSTRACT FROM AUTHOR]

UHRF1 (ubiquitin like with plant homeodomain and ring finger domains 1) is an epigenetic modifier that is overexpressed in some cancers, including pancreatic cancer, and mediates silencing of tumor suppressor genes. However, the role of UHRF1 in regulating pancreatic cancer metabolism and metastasis is not clear. In the present study, we demonstrated that silencing UHRF1 significantly inhibited aerobic glycolysis in pancreatic cancer cells. Furthermore, we demonstrated that UHRF1 knockdown decreased hypoxia inducible factor (HIF)1α levels and HIF1α targeted glycolytic genes. The Cancer Genome Atlas dataset analysis supported this observation. The Sirtuin (SIRT) family members regulate aerobic glycolysis in many cancers. We analyzed the correlation between UHRF1 and SIRT3-5 expression and found a significant negative correlation between UHRF1 and SIRT4. Further transcriptional and functional analysis demonstrates that SIRT4 is a downstream target of UHRF1 and negatively regulated aerobic glycolysis, cell proliferation and tumor growth. Our study identified a novel UHRF1/SIRT4 axis in regulation of pancreatic cancer cell proliferation, metabolism, and metastasis. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a rapidly progressing disease with a poor prognosis. We still have many questions about the pathogenesis, early diagnosis and precise treatment of this disease. Organoids, a rapidly emerging technology, can simulate the characteristics of pancreatic tumors. Using the organoid model of pancreatic cancer, we can study and explore the characteristics of pancreatic cancer, thereby effectively guiding clinical practice and improving patient prognosis. This review introduces the development of organoids, comparisons of organoids with other preclinical models and the status of organoids in basic research and clinical applications for pancreatic cancer. Unlabelled Image [ABSTRACT FROM AUTHOR]