Colorectal cancer (CRC) is a highly invasive malignant tumor. At present, the combination of surgery with chemotherapy constitutes the predominant strategy in the treatment of CRC. The serious side effects of chemotherapy profoundly impair patients’ quality of life. It is of great importance to develop novel approach to reduce side effects and increase anti-tumor efficacy in CRC treatment. Bortezomib (Btz), a reversible proteasome inhibitor, possessing both chemotherapeutic and immunotherapeutic effects by inducing cell pyroptotic. However, the application of Btz is impeded by their lack of tumor-targeting capability and lipid solubility. To address these restrictions and develop an ideal drug carrier, we performed a biohybrid approach by fusing liposomes with artificial extracellular vesicles engineered from cancer cells to generate hybrid liposomes (HV@Btz) for the targeted delivery of Btz. In contrast to liposomes, HV@Btz possessed higher cellular uptake efficiency and strong cytotoxicity against CT26 cells by inducing cell pyroptotic. Additionally, HV@Btz had superior tumor-targeting ability and prolonged circulation time. HV@Btz significantly suppressed tumor growth and triggered robust anti-tumor immune response with minimum systemic toxicity in both subcutaneous and orthotopic CRC-bearing mice. This study demonstrated that HV@Btz could serve as a scalable approach by inducing cell pyroptotic for the management of colorectal cancer. Preparation and application of bortezomib (Btz)-loaded hybrid liposome (HV@Btz) for treatment of CRC in mice. This figure was created by Biorender.

Caspase 6 is a pivotal executioner caspase involved in cell death; however, its role in inflammatory bowel disease (IBD) remains incompletely understood. Levels of cleaved caspase 6 were quantified in colonic tissues from IBD patients, and an IBD mouse model was established via DSS induction, incorporating both systemic (Casp6 KO) and IEC-specific knockout (Casp6 cKO) strategies. Single-cell RNA sequencing (scRNA-seq) revealed that Casp6 KO enhanced necroptosis in IECs, reducing intestinal endocrine cells and damaging intestinal stem cells. Both in vivo and in vitro studies confirmed that caspase 6 deficiency activates the necroptosis pathway by upregulating RIPK1 in IECs and impairs macrophage bacterial clearance. Importantly, Casp6 KO reduces bactericidal activity in a cathepsin L (CTSL)-dependent manner. These findings demonstrate that preserving caspase 6 activity is essential for necroptosis prevention and effective bacterial clearance, providing new insights for future IBD therapies.

During severe acute pancreatitis (SAP), the circulating free fatty acid levels are elevated, and this elevation correlates with a poor prognosis. However, the precise mechanisms by which lipid metabolism influences the progression of SAP remain unclear. Considering that stearoyl-CoA desaturase (SCD1) is a key lipid-modifying enzyme, we investigated its role in SAP. Using caerulein and ligation-induced SAP models along with RNA sequencing, we found that SCD1 is upregulated in SAP models. Through studies with Scd1 knockout mice and acinar cells, we determined that the absence of SCD1 exacerbates pathological damage and inflammatory responses in SAP model mice while inducing lipid peroxidation and ferroptosis. By employing Sirt-/- mice and a lipid metabolomic analysis, we found that SIRT1 upregulates SCD1 expression through deacetylation, thereby contributing to ferroptosis resistance by altering the fatty acid composition. By examining the effects of monounsaturated fatty acids (palmitoleic acid) on SCD1 siRNA-transfected cells, we observed that MUFAs can counteract lipid peroxidation and promote SIRT1 expression, forming a positive feedback loop that resists ferroptosis in SAP model mice. Our findings indicate that SCD1-mediated cellular lipid and redox homeostasis plays a key role in SAP defense, suggesting a potential mechanism for SAP prevention and treatment.

SN-38 is the active metabolite of irinotecan and acts as an effective topoisomerase I inhibitor with therapeutic effects on many malignant tumors, including some drug-resistant cancers. However, the poor solubility, low bioavailability, and severe dose-dependent toxicity limits the clinical application of SN-38. Currently, emerging macrophage membrane-coated nanoparticles provide an efficient biomimetic approach to develop novel SN-38 formulations for the reduction of its side effects. Photothermal therapy (PTT) is a promising methods in tumor treatment to thermally ablate tumors using various materials such Prussian blue nanoparticles (NPs) and can combined with chemotherapy to synergistically work. There is no report that combined SN38 and photothermal therapy for the treatment of colorectal cancer (CRC). SN38-PB@CM NPs were constructed by loading SN-38 into macrophage cell membrane-coated hollow mesoporous Prussian blue (PB) NPs. The morphology, size and zeta potential were evaluated by transmission microscopy and dynamic light scatter (DLS). Coomassie bright blue staining was performed to assess total protein profile. The photothermal properties of it were also investigated via near-infrared imaging. CCK8 and calcein-AM/PI staining were used to evaluate cell viability. Flow cytometry was performed to assess cell apoptosis. The fluorescent microscopy was used to observe cellular uptake of SN38-PB@CM NPs to assess its internalization in vitro. The biodistribution, tumor-targeting efficacy, antitumor efficacy and safety of SN38-PB@CM NPs in vivo were assessed in CT26 tumor-bearing mice via In Vivo Imaging System. SN38-PB@CM NPs were successfully constructed and exhibited a uniform size distribution (140.5 ± 4.3 nm) and an excellent drug-loading capacity (5.61 ± 0.64

The effect of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a persistent environmental pollutant commonly used as a flame retardant in various consumer products, on pancreatitis has not been clearly elucidated, although it has been reported to be toxic to the liver, nervous system, and reproductive system. Acute pancreatitis (AP) and chronic pancreatitis (CP) models were induced in this study by intraperitoneal injection of caerulein. The aim was to investigate the impact of BDE-47 on pancreatitis by exposing the animals to acute (1 week) or chronic (8 weeks) doses of BDE-47 (30 mg/kg in the low-concentration group and 100 mg/kg in the high-concentration group). Additionally, BDE-47 was utilized to stimulate mouse bone marrow-derived macrophages, pancreatic primary stellate cells, and acinar cells in order to investigate the impact of BDE-47 on pancreatitis. In vivo experiments conducted on mice revealed that chronic exposure to BDE-47, rather than acute exposure, exacerbated the histopathological damage of AP and CP, leading to elevated fibrosis in pancreatic tissue and increased infiltration of inflammatory cells in the pancreas. In vitro experiments showed that BDE-47 can promote the expression of the inflammatory cytokines Tnf-α and Il-6 in M1 macrophages, as well as promote acinar cell apoptosis through the activation of the PERK and JNK pathways via endoplasmic reticulum stress. The findings of this study imply chronic exposure to BDE-47 may exacerbate the progression of both AP and CP by inducing acinar cell apoptosis and dysregulating inflammatory responses.

Background: SN-38, recognized as the primary active derivative of the pivotal chemotherapeutic agent CPT-11, demonstrates substantially enhanced efficacy in colorectal cancer (CRC) management compared to CPT-11. Nonetheless, challenges such as low stability, inadequate aqueous solubility, limited bioavailability, and nonspecific targeting to cancer cells hinder its clinical adoption. In the present research, we synthesized SN-38loaded liposomes cloaked with macrophage membranes (SN-38@MM-LPs) to assess their therapeutic potential and safety profile in addressing CRC. Methods: SN-38@MM-LPs were synthesized using an incubation extrusion technique, combining a macrophage membrane with liposomes (LPs). It was characterized by size, zeta potential, transmission electron microscopy observations, polydispersity index and coomassie bright blue staining. CCK-8, EdU, and flow cytometry assays were performed to evaluate the viability and apoptosis rates of HCT116 and HCT8 cells after treatment with SN38@MM-LPs. A cellular uptake assay was conducted to evaluate the internalization of SN-38@MM-LPs in vitro. Moreover, the biodistribution, therapeutic efficacy, and safety of SN-38@MM-LPs were further assessed in orthotopic HCT116 xenograft model mice. Results: Characterization results revealed that SN-38@MM-LPs possess a spherical morphology with a consistent size distribution (129 nm) and a drug loading efficiency of 5.54 +/- 0.73%. SN-38 curtailed the growth and promoted apoptosis in both HCT8 and HCT116 cells. The impact of SN-38 was accentuated when delivered via SN-38@LPs and SN-38@MM-LPs. Notably, in the orthotopic xenograft model, SN-38@MM-LPs manifested superior tumor-targeting capabilities and therapeutic outcomes. Additionally, SN-38@MM-LPs presented negligible hepatic toxicity. Conclusions: SN-38@MM-LPs showcased potent and targeted antitumor actions in CRC. Consequently, SN38@MM-LPs emerge as a potential nanoparticle formulation that could amplify the antitumor efficacy of SN38, simultaneously mitigating liver toxicity concerns.

Proteins that recognize epigenetic modifications function as mediators to interpret epigenetic codes. Hypoxia response and metabolic rewiring are two major events during cancer progression. However, whether and how the epigenetic regulator integrates hypoxia response and metabolism together remain open for study.We data mined the clinical association of 33 histone lysine acetylation reader proteins with liver cancer and found that ALL1-fused gene from chromosome 9 (AF9) is up-regulated in cancer and correlates with tumor stage and poor prognosis. Conditional deletion of Af9 in mouse liver resulted in decreased tumor formation induced by c-MET proto-oncogene/β-catenin. Loss of AF9 heavily impaired cell proliferation and completely blocked solid tumor formation. We further discovered that AF9 formed a positive feedback circuit with hypoxia-inducible factor 1 alpha (HIF1α) and also stabilized MYC proto-oncogene (cMyc). Mechanically, AF9 interacted with HIF1α and targeted HIF1A promoter whereas AF9 recognized cMyc acetylation at K148, protected cMyc phosphorylation at S62, and then stabilized cMyc, which, in turn, up-regulates phosphofructokinase, platelet expression. Otherwise, knockout of Af9 in mouse hepatocytes increased the infiltration of CD8+ T cells, which is linked to the down-regulation of lactate dehydrogenase A.AF9 is up-regulated to promote gene expression of hypoxia tolerance and glycolysis by simultaneously forming a complex with HIF1α and recognizing acetylated cMyc. Our results establish the oncogenic role of AF9 in human liver cancer, which could be a potential target for designing drugs against liver cancer.

Colorectal cancer (CRC) is the most frequently diagnosed cancer of the digestive tract.Chemotherapy drugs such as oxaliplatin are frequently administered to CRC patients diagnosed with advanced or metastatic disease.A deep understanding of the molecular mechanism underlying CRC tumorigenesis and identification of optimal biomarkers for estimating chemotherapy sensitivity are essential for the treatment of CRC.Numerous members of the kinesin family are dysregulated in cancers, contributing to tumorigenesis, metastasis and drug resistance.KIF11 is a key component of the bipolar spindle and is highly expressed in several cancer types.We analyzed KIF11 expression in clinical samples by Western blotting and qRT-PCR and explored its role and mechanism in CRC growth and sensitivity to oxaliplatin via detection of the phosphorylation profile of kinases and gain-and-loss-of-function assays.We found that KIF11 was upregulated in CRC tissues and was associated with advanced clinical stage and vessel invasion and that knockdown of KIF11 led to tumor growth arrest and increased sensitivity to oxaliplatin via enhanced DNA damage and apoptosis.Mechanistically, aberrantly activated p53 signaling or possibly deactivated GSK3β signaling was responsible for KIF11 knockdown-mediated effects in CRC cells.Thus, our data firmly demonstrated that KIF11 could serve as a potential oncogene and proper biomarker for assessing oxaliplatin sensitivity in CRC.

Pancreatic cancer is a highly malignant cancer of the pancreas with a very poor prognosis. Methylation of histone lysine residues is essential for regulating cancer physiology and pathophysiology, mediated by a set of methyltransferases (KMTs) and demethylases (KDMs). This study surveyed the expression of methylation regulators functioning at lysine 9 of histone 3 (H3K9) in pancreatic lesions and explored the underlying mechanisms. We analyzed KDM1A and KDM3A expression in clinical samples by immunohistochemical staining and searching the TCGA PAAD program and GEO datasets. Next, we identified the variation in tumor growth in vitro and in vivo after knockdown of KDM1A or KDM3A and explored the downstream regulators of KDM1A and KDM3A via RNA-seq, and gain- and loss-of-function assays. Eleven H3K9 methylation regulators were highly expressed in pancreatic cancer, and only KDM1A and KDM3A expression positively correlated with the clinicopathological characteristics in pancreatic cancer. High expression of KDM1A or KDM3A positively correlated with pathological grade, lymphatic metastasis, invasion, and clinical stage. Kaplan-Meier analysis indicated that a higher level of KDM1A or KDM3A led to a shorter survival period. Knockdown of KDM1A or KDM3A led to markedly impaired tumor growth in vitro and in vivo. Mechanistically, CCNA2, a cell cycle-associated gene was partially responsible for KDM1A knockdown-mediated effect and CDK6, also a cell cycle-associated gene was partially responsible for KDM3A knockdown-mediated effect on pancreatic cancer cells. Our study demonstrates that KDM1A and KDM3A are highly expressed in pancreatic cancer and are intimately correlated with clinicopathological factors and prognosis. The mechanism of action of KDM1A or KDM3A was both linked to the regulation of cell cycle-associated genes, such as CCNA2 or CDK6, respectively, by an H3K9-dependent pathway.

Background: To evaluate the pattern and prevalence trends of liver cirrhosis caused by specific etiologies. Results: Globally, the number of prevalent cases increased 74.53% from 1990 to 2017. The ASR increased 0.75 per year. The most pronounced increases were found in middle-high and high socio-demographic index (SDI) regions, especially in the Caribbean and Latin America. Among the etiologies, non-alcoholic steatohepatitis (NASH) related liver cirrhosis accounted for 59.46% of the cases. The ASR increased 1.74 per year, and the increase was observed in all 5 SDI regions. In addition, the ASR of liver cirrhosis caused by alcohol also increased in both sexes and all SDI regions. In contrast, the ASR of liver cirrhosis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) decreased, especially in middle and low-middle SDI regions. Conclusions: Though the number of people suffering from HBV and HCV decreases, liver cirrhosis is still a major threat to health. Additionally, the number of people with cirrhosis caused by alcohol and NASH continues to grow. Thus, more targeted and specific strategies should be established based on etiology and prevalence trends of liver cirrhosis. Methods: We collected data based on Global Burden of Disease (GBD) 2017 study. The age standardized prevalence rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the trends in prevalence by population, etiologies and regions.

Pancreatic cancer (PC) is the most malignant cancer type in the digestive system with a poor prognosis. Chemotherapy such as cisplatin is the last chance for PC patients diagnosed with advanced or metastatic disease. Obtaining a deep understanding of the molecular mechanism underlying PC tumorigenesis and identifying optimal biomarkers to estimate chemotherapy sensitivity are essential for PC treatment. The chromatin remodeler HELLS was found to regulate various tumor suppressors through an epigenetic pathway in several cancers. We analyzed HELLS expression in clinical samples by Western blotting and immunohistochemical staining. Next, we identified the variation in tumor growth and cisplatin sensitivity after knockdown of HELLS and explored the downstream mediators of HELLS in PC via RNA-seq, chromatin immunoprecipitation, and gain- and loss-of-function assays. We found that HELLS is upregulated in PC tissues and correlates with advanced clinical stage and a poor prognosis, and the knockdown of HELLS leads to tumor growth arrest and increased sensitivity to cisplatin. Mechanistically, the tumor suppressor TGFBR3 is markedly reexpressed after HELLS knockdown; conversely, compromising TGFBR3 rescues HELLS knockdown-mediated effects in PC cells. Thus, our data provide evidence that HELLS can serve as a potential oncogene and suitable biomarker to evaluate chemotherapy sensitivity via epigenetically silencing the tumor suppressor TGFBR3 in PC.

Acinar cell injury and the inflammatory response are critical bioprocesses of acute pancreatitis (AP). We investigated the role and underlying mechanism of sulfiredoxin-1 (Srxn1) in AP. Mild AP was induced by intraperitoneal injection of cerulein and severe AP was induced by partial duct ligation with cerulein stimulation or intraperitoneal injection of L-arginine in mice. Acinar cells, neutrophils, and macrophages were isolated. The pancreas was analyzed by histology, immunochemistry staining, and TUNEL assays, and the expression of certain proteins and RNAs, cytokine levels, trypsin activity, and reactive oxygen species (ROS) levels were determined. Srxn1 was inhibited by J14 or silenced by siRNA, and overexpression was introduced by a lentiviral vector. Transcriptomic analysis was used to explore the mechanism of Srxn1-mediated effects. We also evaluated the effect of adeno-associated virus (AAV)-mediated overexpression of Srxn1 by intraductal administration and the protection of AP. We found that Srxn1 expression was upregulated in mild AP but decreased in severe AP. Inhibition of Srxn1 increased ROS, histological score, the release of trypsin, and inflammatory responses in mice. Inhibition of Srxn1 expression promoted the production of ROS and induced apoptosis, while overexpression of Srxn1 led to the opposite results in acinar cells. Furthermore, inhibition of Srxn1 expression promoted the inflammatory response by accumulating and activating M1 phenotype macrophages and neutrophils in AP. Mechanistically, ROS-induced ER stress and activation of Cathepsin B, which converts trypsinogen to trypsin, were responsible for the Srxn1 inhibition-mediated effects on AP. Importantly, we demonstrated that AAV-mediated overexpression of Srxn1 attenuated AP in mice. Taken together, these results showed that Srxn1 is a protective target for AP by attenuating acinar injury and inflammation through the ROS/ER stress/Cathepsin B axis.

Nonalcoholic steatohepatitis (NASH) has rapidly become the most common cause of chronic liver diseases. We aimed to explore the incidence and distribution characteristics of NASH by sex, region and sociodemographic index (SDI). We collected data, including sex and region, on NASH-related liver cirrhosis from the 2017 GBD study. The age-standardized incidence rates (ASRs) and estimated annual percentage changes (EAPCs) were used to estimate the incidence trend and distribution characteristics. Globally, the incidence of liver cirrhosis caused by NASH increased from 178,430 cases in 1990 to 367,780 cases in 2017, an increase of approximately 105.56%. The ASR of NASH increased by an average of 1.35% per year (95% CI 1.28-1.42). Meanwhile, large differences in the ASR and the EAPC were observed across regions. The middle-high SDI region had the highest increase among all five SDI regions, followed by middle SDI region. In addition, Eastern Europe, Andean Latin America and Central Asia showed a more significant growth trend of ASR. In contrast, the high SDI region demonstrated the slowest increasing trend of ASR, and the high-income Asia Pacific demonstrated a decreasing trend among the 21 regions. Liver cirrhosis has caused a huge and rising health burden in many countries and regions. In addition, with the growth of obesity, population and aging, NASH might replace viral hepatitis as the most important cause of liver cirrhosis in the near future. Therefore, appropriate interventions are needed in coming decades to realize early diagnosis and prevention of NASH-related liver cirrhosis.

In this work, through utilizing the mixed-ligand synthesis method, two coordination polymers (CPs) based on Co(II), namely, {[Co(μ-ppda)(μ-pbmeix)]·H2O}n (2) and [Co(μ-opda)(μ-pbmeix)0.5]n (1), have been triumphantly formed from 1,4-bis(2-methylimidazol-1-ylmethyl)benzene (pbmeix), a semi-rigid ligand with Co(II) nitrate salts and distinct carboxylic acid co-ligands (o/ppda = 1,2-/1,4-phenylenediacetate). For treatment of pancreatic cancer, the as-generated compounds’ inhibitory activity against the viability of cancer cell was determined by the Cell Counting Kit-8 (CCK-8) assay. The above compounds’ suppression effect against the cells invasion and migration ability was investigated by the trans-well detection. The real time reverse transcription-polymerase chain reaction (RT-PCR) subsequently was employed to test the VEGF signaling pathway activation. Eventually, the cancer cells apoptosis levels after treating with above compound were assessed via detecting the BCL-2 protein expression level. Furthermore, results from molecular docking simulation indicate that complex 1 not only exhibits relatively lower affinity energy, but also forms more binding interactions in comparison to complex 2 when binding to a given target protein. Complex 1 was much superior to complex 2 on treating pancreatic cancer via suppressing the cancer cell invasion, migration and viability ability.

The Editors of JBUON issue an Expression of Concern to 'Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway', by Shijian Yi, Guowen Liu, Yang Wu, Qiankun Liang, Lanlan Li; JBUON 2020;25(1):389-394; PMID: 32277659. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

PURPOSE:Pancreatic cancer (PC) is a lethal disease of the alimentary system and is ranked 4th in cancer-related deaths in United States. PC has a poor prognosis and limited therapeutic options. The main purpose of the current study was to demonstrate the anticancer effects of the naturally occurring Baicalein flavone in human cisplatin-resistant pancreatic carcinoma cell line CAPAN-2.METHODS:Cell viability was examined via MTT cell proliferative assay. Mitochondrial-mediated apoptosis was examined through DAPI and annexin V/propidium iodide (PI) staining using fluorescence microscopy along with estimation of apoptosis-related protein expressions like caspase-3, Bax, Bcl-2 for which western blot was used. Next, wound-healing and transwell assays were performed to find out the effects of Baicalein on cell migration and invasion, respectively.RESULTS:The results showed that Baicalein induced dose-dependent and selective anticancer effects in CAPAN-2 PC cancer cells with much less cytotoxicity to normal HTRET-HPNE cells. The antiproliferative effects of Baicalein were due to apoptosis induction as the number of apoptotic cells increased on increasing doses of the test molecule. Western blotting analysis revealed that the expressions of caspase-3 and Bcl-2 were decreased and Bax was increased. The test molecule also induced S-phase cell cycle arrest in PC cells with decreasing the cyclin-B1 expressions. Cell migration and invasion analysis revealed that Baicalein induced dose-dependent suppression in migration and invasion of CAPAN-2 PC cell line.CONCLUSION:Baicalein is a potential anticancer agent against PC cells and can be considered for PC systemic therapy provided more toxicological and in vivo studies are carried out.

Pancreatic cancer is a leading cause of cancer-related death worldwide. Cisplatin is an essential drug treating patients with BRCA1/2 or PALB2 mutations. Whether other genetic determinants of cisplatin sensitivity exist and their underlying mechanisms remain unclear. Immunohistochemistry was used to determine METTL14 expression in pancreatic cancer tissues and non-tumoural tissues. Cell proliferation was detected with CCK-8 assays. Apoptosis was analysed via Western blotting and flow cytometry, and autophagy was analysed via Western blotting and immunofluorescence. In this work, we found higher METTL14 expression in pancreatic cancer tissues than in non-tumoural tissues, and METTL14 expression was associated with pathological characteristics. Downregulation of METTL14 with siRNA sensitized pancreatic cancer cells to cisplatin. Specifically, apoptosis and autophagy were significantly enhanced in METT14 knockdown cells compared with control cells after treatment with cisplatin. Mechanistically, the AMPKα, ERK1/2 and mTOR signalling pathways were disturbed by downregulation of METTL14. We further found that METTL14 knockdown-mediated autophagy was dependent on mTOR signalling and that mTOR activation decreased autophagy to the level observed in the control group. Collectively, our results indicate that METTL14 is upregulated in pancreatic cancer, downregulation of METTL14 sensitizes pancreatic cancer cells to cisplatin by enhancing apoptosis, and autophagy is improved via an mTOR signalling-dependent pathway.

The role of lncRNAs in the regulation of glutamate metabolism and metabolic reprogramming of pancreatic cancer (PC) during nutrient deprivation is largely unknown. Our study found that alpha-ketoglutarate (aKG) levels were significantly reduced in the absence of XLOC_006390. We subsequently confirmed that the decrease in aKG was mainly due to the downregulation of glutamate dehydrogenase 1 (GDH1) at the mRNA level. Therefore, we first screened transcription factors targeting the GDH1 gene promoter and confirmed that c-Myc regulates GDH1 transcription. c-Myc binds to the promoter of GDH1 and activates its transcription. Downregulation of GDH1 mRNA levels by XLOC_006390 deletion could be rescued by overexpression of c-Myc. Overexpression of XLOC_006390 promoted the protein stability of c-Myc by blocking its ubiquitination. Clinically, XLOC_006390 was positively correlated with the mRNA level of GDH1, and c-Myc positively regulated GDH1 gene expression, which was tightly associated with PC patient prognosis. The dysregulated lncRNA/c-Myc axis increased glutamate metabolism, promoting PC progression to a higher stage. Therefore, XLOC_006390/c-Myc may be a potential target for PC, and its abnormal activation also indicates the progression of PC.

Radio-resistance is a growing concern in treating patients with pancreatic cancer (PC). Here we investigated the role of miR-590-5p in the radio-resistance of PC cells. We developed radioresistant PC cell lines and followed by microarray analysis and levels of miRs compared to parental cell lines. PC cells were transfected using either miR mimics or inhibitors followed by clonogenic survival assays. We also studied the effect of miR-590-5p on autophagy using electron microscopy and immunoblot analysis. In addition, the luciferase assay was used to identify potential targets. The radio-resistant PC cells exhibited decreased expression of miR-590-5p, with elevated autophagy against the parental cells. The over-expression of miR-590-5p inhibited radiation-mediated autophagy, while inhibitors induced autophagy in PC cells. The up-regulation of miR-590-5p enhanced the radio-sensitivity of PC cells. We confirmed ATG-3 as a target of miR-590-5p, whose levels were unregulated in radio-resistant cells. We also found that levels of ATG-3 were associated with autophagy. Expression of miR-590-5p inhibited radiation-mediated autophagy and enhanced the radio-sensitivity of PC cells.