👤 Fachen Zhou

Renal interstitial fibrosis (RIF) is a pathological process that fibrotic components are excessively deposited in the renal interstitial space due to kidney injury, resulting in impaired renal function and chronic kidney disease. The molecular mechanisms controlling renal fibrosis are not fully understood. In this present study, we identified Nuclear protein 1 (Nupr1), a transcription factor also called p8, as a novel regulator promoting renal fibrosis. Unilateral ureteral obstruction (UUO) time-dependently induced Nupr1 mRNA and protein expression in mouse kidneys while causing renal damage and fibrosis. Nupr1 deficiency (Nupr1 Show less

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal cancers in the world. Dysregulation of purine-rich element binding protein alpha (PURα), which contributes to the initiation of PURΑ syndrome, is reportedly involved in the progression of multiple cancers, but its function and underlying mechanisms in ESCC progression remain unclear. Here, we first demonstrated that PURα promoted cell growth, migration and invasion in ESCC both in vitro and in vivo. An immunohistochemistry assay was then performed on 225 ESCC tissues, showing that high PURα expression was positively associated with lymph node metastasis and the AJCC stage, and the ESCC patients with positive PURα expression had worse survival. In addition, RNA sequencing implied that PURα induced epithelial-mesenchymal transition (EMT) in ESCC, which was further confirmed by qPCR, Western blotting and immunofluorescence analyses. Mechanistically, PURα enhanced the transcription of Snail2 by binding to its promoter region. Knockdown of Snail2 reversed PURα-induced EMT and inhibited the migration and invasion of ESCC cells. In conclusion, this study indicated that PURα promotes Snail2 transcriptional activity to induce EMT during ESCC progression. Show less

Long noncoding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression; however, the mechanism by which aberrantly expressed lncRNA RP11-84E24.3 regulates the pathogenesis of glioma is not fully understood. Here, we investigate the function of lncRNA RP11-84E24.3 in glioma onset and progression as well as identify a molecular pathway regulated by this lncRNA. Differentially expressed lncRNAs related to glioma were identified. The aberrant expression of lncRNA RP11-84E24.3 was verified in samples from patients with glioma as well as glioma cell lines. The role of lncRNA RP11-8424.3 in proliferation, apoptosis, migration, and invasion was assessed using gain- and loss-of function approaches, EdU incorporation, flow cytometry, wound healing and Transwell invasion assays. Western blot analysis was utilized to examine the expression of proteins associated with epithelial-to-mesenchymal transition (EMT). The interaction between lncRNA RP11-84E24.3, TFAP2C and SNAI1 was confirmed using RNA pull-down, ChIP and luciferase reporter assays. LncRNA RP11-84E24.3 was up-regulated in both glioma tissues and cell lines. LncRNA RP11-84E24.3 overexpression enhanced the proliferation, migration and invasion of glioma cells while reducing apoptosis. This was associated with a decrease in E-cadherin expression and an increase in N-cadherin and Vimentin expression. LncRNA RP11-84E24.3 directly targeted TFAP2C protein, resulting in increased SNAI1 expression. Knockdown of TFAP2C or SNAI1 reversed the effects of lncRNA RP11-84E24.3 overexpression, while silencing lncRNA RP11-84E24.3 inhibited tumor formation of glioma cells in vivo. LncRNA RP11-84E24.3 increased SNAI1 expression by forming a complex with TFAP2C protein, promoting EMT in glioma cells and tumor formation. Show less

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and due to its complex pathogenic factors, its prognosis is poor. N6-methyladenosine (m The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI-JP samples, respectively, were used in this study. Both the expression of SNRPC in HCC was upregulated in the TCGA and ICGC databases compared to normal tissues. Next, the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By gene set variation (GSVA) analysis and gene set enrichment (GSEA) analysis, we found that SNRPC was mainly related to protein metabolism and the immune process. Furthermore, the estimation of stromal and immune cells in malignant tumor tissues using expression (ESTIMATE), microenvironment cell population counter (MCP-counter), and single sample GSEA (ssGSEA) algorithms revealed that the high-SNRPC group had a lower stromal score, lower abundance of endothelial cells and fibroblasts, and lower immune infiltration. Ultimately, a tumor immune dysfunction and exclusion (TIDE) analysis revealed that patients in the low-SNRPC group may be more sensitive to immune checkpoint inhibitor therapy. SNRPC could serve as a promising prognostic and immunotherapeutic marker in HCC and might contribute to new directions and strategies for HCC treatment. Show less

Radiotherapy is one of the main strategies for the treatment of esophageal squamous cell carcinoma (ESCC). However, treatment failure often occurs due to the emergence of radioresistance. In this study, we report a key regulator of radiation sensitivity, termed TAB182 that may become an ideal biomarker and therapeutic target to overcome radioresistance. By applying qRT-PCR and immunohistochemical staining, the expression of TAB182 was detected in patient tissues. We next assessed the influence of TAB182 downregulation to radiosensitivity using clonogenic survival assay and γ-H2A.X foci analysis in TE-1, TE-10, and radioresistant TE-1R cell lines after ionizing radiation. To unveil the mechanism underlying, TAB182 interacting proteins were identified by mass spectrometry following co-immunoprecipitation. Furthermore, flow cytometry and western blot assay were applied to validate the identified proteins. Our results demonstrated that the expression of TAB182 is higher in cancer tissues than normal tissues and elevated expression of TAB182 correlates with poor outcomes of postoperative radiotherapy. Downregulation of TAB182 sensitized cancer cells to ionizing radiation, particularly in radioresistant TE-1R cells that spontaneously overexpress TAB182. Mechanically, TAB182 interacts with FHL2 to induce G2-M arrest through wiring the CHK2/CDC25C/CDC2 signaling pathway. Finally, overexpression of shRNA-resistant TAB182 restored the checkpoint and radioresistance. TAB182 potentiates the radioresistance of ESCC cells by modulating the G2-M checkpoint through its interaction with FHL2. Thus, TAB182 may become an ideal biomarker and therapeutic target of ESCC radiotherapy. Show less

Parkinson's disease (PD) is a complex neurodegenerative disorder with a strong genetic component. A growing number of variants and genes have been reported to be associated with PD; however, there is no database that integrate different type of genetic data, and support analyzing of PD-associated genes (PAGs). By systematic review and curation of multiple lines of public studies, we integrate multiple layers of genetic data (rare variants and copy-number variants identified from patients with PD, associated variants identified from genome-wide association studies, differentially expressed genes, and differential DNA methylation genes) and age at onset in PD. We integrated five layers of genetic data (8302 terms) with different levels of evidences from more than 3,000 studies and prioritized 124 PAGs with strong or suggestive evidences. These PAGs were identified to be significantly interacted with each other and formed an interconnected functional network enriched in several functional pathways involved in PD, suggesting these genes may contribute to the pathogenesis of PD. Furthermore, we identified 10 genes were associated with a juvenile-onset (age ≤ 30 years), 11 genes were associated with an early-onset (age of 30-50 years), whereas another 10 genes were associated with a late-onset (age > 50 years). Notably, the AAOs of patients with loss of function variants in five genes were significantly lower than that of patients with deleterious missense variants, while patients with Show less

Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro. Show less

Chronic elevated free fatty (FFA) levels are linked to metabolic disorders and tumorigenesis. However, the molecular mechanism by which FFAs induce cancer remains poorly understood. Here, we show that the tumor suppressor PTEN protein levels were decreased in high fat diet (HFD) fed mice. As palmitic acid (PA, C16:0) showed a significant increase in the HFD fed mice, we further investigated its role in PTEN down regulation. Our studies revealed that exposure of cells to high doses of PA induced mTOR/S6K-mediated phosphorylation of PTEN at T366. The phosphorylation subsequently enhanced the interaction of PTEN with the E3 ubiquitin ligase WW domain-containing protein 2 (WWP2), which promoted polyubiquitination of PTEN and protein degradation. Consistent with PTEN degradation, exposure of cells to increased concentrations of PA also promoted PTEN-mediated AKT activation and cell proliferation. Significantly, a higher level of S6K activation, PTEN T366 phosphorylation, and AKT activation were also observed in the livers of the HFD fed mice. These results provide a molecular mechanism by which a HFD and elevated PA regulate cell proliferation through inactivation of tumor suppressor PTEN. Show less

Melanocortin-4 receptor (MC4R) was considered as an essential modifiers in feelings intake, the regulation of metabolism and body weight. This study aimed at identifying polymorphisms in MC4R gene that might associate with carcass quality traits in Chinese indigenous beef cattle breed. qPCR analysis showed that the MC4R gene was widely expressed in various tissues, with predominantly expression levels in heart. Three single-nucleotide polymorphisms (SNPs) were identified, including a mutation (g.85A > G) in 5'untranslated regions (UTR) and two mutations (g.927C > T and g.1069C > G) in exon 1. Based on the χ Show less

The bHLH transcription factor Olig2 is required for sequential cell fate determination of both motor neurons and oligodendrocytes and for progenitor proliferation in the central nervous system. However, the role of Olig2 in peripheral sensory neurogenesis remains unknown. We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice, associated with significantly diminished expression of multiple OSN maturation and odorant signaling genes, including Omp, Gnal, Adcy3, and Olfr15. We further demonstrate that Olig2 binds to the E-box in the Omp promoter region to regulate its expression. Taken together, our results reveal a distinctly novel function of Olig2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons. Show less

Increasing evidence shows that Angptl4 affects proteinuria in podocytes injured kidney disease, however, whether there is a relationship between Angptl4 and IgA nephropathy (IgAN) has not been studied yet. Plasma and urine samples were obtained from 71 patients with IgAN and 61 healthy controls. Glomeruli from six renal biopsy specimens (three IgAN patients and three healthy controls) were separated by RNA-Seq. Differentially expressed genes (DEGs) related to podocytes and Angptl4 between IgAN patients and healthy controls were performed using the Limma package. Gene set enrichment analysis was used to determine whether there was a statistically significant difference between the two groups. STRING was used to create a protein-protein interaction network of DEGs. Association analysis between Angptl4 levels and clinical features of IgAN was performed. Thirty-three podocyte-related and twenty-three Angpt4-related DEGs were found between IgAN patients and healthy controls. By overlapping the genes, Our findings show that Angptl4 levels in plasma and urine are related to podocyte damage and, therefore, may be a promising tool for assessing the severity of IgAN patients to identify and reverse the progression to ESRD. Show less

Epigenetic regulation of gene expression has been reported in the pathogenesis of metabolic disorders such as diabetes and liver steatosis in humans. However, the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in chickens have been rarely studied. H3K27ac chromatin immunoprecipitation coupled with high-throughput sequencing and high-throughput RNA sequencing was performed to compare genome-wide H3K27ac profiles and transcriptomes of liver tissue between healthy and FLHS chickens. In total, 1,321 differential H3K27ac regions and 443 differentially expressed genes were identified (| log2Fold change| ≥ 1 and Show less

The resistance of cancer cells to carboplatin restricts their efficacy in the clinical setting, and a solution to reverse the resistance is urgently required for the treatment of ovarian cancer. An increasing number of studies have found associations between obesity and the incidence, and mortality rates of female cancer. However, the association between adipocytes and the resistance of ovarian cancer has rarely been reported. Based on this, the present study first revealed the inductive effect of adipocytes on the resistance of ovarian cancer to carboplatin using in vivo and in vitro experiments. Subsequently, it was identified that the angiopoietin‑like 4 (ANGPTL4) secreted by adipocytes played a vital role in the resistance of ovarian cancer using bioinformatics analysis, cellular and molecular biological experiments, as well as forward and backward validation. The glycosylated ANGPTL4 protein could bind with integrin α5β1 on the surface of ovarian cancer cells; following which, it could activate the c‑myc/NF‑κB pathway and stimulate the expression of the antiapoptotic protein Bcl‑xL, as well as the ABC transporter family members ABCB1, ABCC1 and ABCG2. Thus, inducing the resistance of ovarian cancer to carboplatin. In conclusion, targeting the adipocyte‑derived ANGPTL4 combined with the application of carboplatin contributes to the clinical treatment for ovarian cancer. Show less

The Editors-in-Chief have retracted this article [1] following an investigation by the University of Maryland. The institution found that in Figure 1C, the graph showing PDGF-B does not match the original data for the 24-hour time point. The graph shows the value to be over 1000 pg/ml, but the original data have a value of 106.626. In Figure 1F, the data were entered manually to create the standard deviation bars. The data manually entered do not match the original data. When the standard deviations for the original data were calculated, the p values were no longer significant using a paired student t test. In Figure 2C, the original data do not match the published data. In Figure 4B, the images in the first lane and the fifth lane are from the same micrograph (i.e., the same set of conditions). However, the published figure claims that they are different conditions. The metadata in this figure also shows different cell lines than those noted in the article. The first and last images are labelled as "Du145 shAR3 anti AR3.jpg". The second image is labelled as "Du145 shAR8 anti AR8.jpg". The third image is labelled as "Cos1 mARs3 mS3-2 antibody-2.jpg." The fourth image is labelled as "R1 3634 bleed.jpg". Due to these errors, the Editors-in-Chief have found that the results are no longer reliable. Show less

Hypoxia induces a vast array of long noncoding RNAs (lncRNA) in breast cancer cells, but their biological functions remain largely unknown. Here, we identified a hitherto uncharacterized hypoxia-induced lncRNA RAB11B-AS1 in breast cancer cells. RAB11B-AS1 is a natural lncRNA upregulated in human breast cancer and its expression is induced by hypoxia-inducible factor 2 (HIF2), but not HIF1, in response to hypoxia. RAB11B-AS1 enhanced the expression of angiogenic factors including VEGFA and ANGPTL4 in hypoxic breast cancer cells by increasing recruitment of RNA polymerase II. In line with increased angiogenic factors, conditioned media from RAB11B-AS1-overexpressing breast cancer cells promoted tube formation of human umbilical vein endothelial cells Show less

Colorectal cancer (CRC) is one of the most aggressive tumours in the human digestive system. Most CRC patients have poor prognosis due to metastasis and recurrence. Angiopoietin-like 4 (ANGPTL4) is involved in tumour development. Regulatory T (Treg) cells and M2 macrophages promote tumour growth and metastasis. Herein, we explored the changes of ANGPTL4 expression in CRC patients at different stages and observed whether in situ tumour-Treg and -M2 macrophages are correlated with ANGPTL4 expression. Serum ANGPTL4 (sANGPTL4) levels of 70 CRC patients and 10 healthy controls were detected by ELISA. ANGPTL4, Foxp3 and CD163 expression levels in CRC tissues were measured by immunohistochemistry. Recombinant ANGPTL4 (rANGPTL4) proteins were further added into cell-culture systems for induction of Treg cells and M2 macrophages. The results showed both sANGPTL4 and in situ tumour-ANGPTL4 expression levels increased in Dukes C-D stage CRC patients. Foxp3 Show less

Carotid atherosclerosis disease (CAD) is generally associated with the occurrence of cardiovascular and cerebrovascular accidents. However, CAD has not been taken seriously enough in the clinic, which, coupled with the single treatment and prevention of CAD, has led to a generally low level of patient compliance. Therefore, acupuncture is expected to be a safe and effective therapy that can be maintained in the long term for patients with CAD. The study objective is to evaluate the efficiency and reliability of acupuncture to relieve CAD and provide a new therapeutic idea for the clinical treatment of CAD. This is a three-arm randomized clinical trial in China. Three groups (TA, SA, and MC) will be randomly allocated at a 1:1:1 ratio. The study will enrol 105 cervical atherosclerosis plaque patients in total on a voluntary basis, with 35 patients in each group. The treatment will last for 12 weeks, with two treatments per week for twenty-four treatments in total. Two 3D ultrasound indicators will be measured as the primary outcomes: the total plaque volume (PV) of the carotid artery on each side and the grey-scale median (GSM). The secondary outcomes will include intima-media thickness (IMT), lipid levels, apolipoprotein A-IV level, platelet count (PLT), fibrinogen (FIB), and platelet aggregation rate (PAR). All the outcomes will be assessed before treatment, after treatment, and after a 12-week follow-up period. This study will utilize per-protocol (PP) and intention-to-treat (ITT) analysis principles. This trial is to evaluate the efficacy and reliability of acupuncture in relieving carotid atherosclerotic plaques by establishing acupuncture (TA), sham acupuncture (SA), and medication (MC) groups. This study was approved by the Institutional Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine (no. YF2018-107-01). All data and findings will be provided by the principal investigator via email. ChiCTR, ChiCTR1800019259 . Registered on 1 November 2018-retrospectively registered, http://www.chictr.org.cn/index.aspx. Show less

Acute pancreatitis in pregnancy (APIP) is a life-threatening disease for both mother and fetus. To date, only three patients with recurrent hypertriglyceridemia-induced APIP (HTG-APIP) have been reported to carry rare variants in the lipoprotein lipase (LPL) gene, which encodes the key enzyme responsible for triglyceride (TG) metabolism. Coincidently, all three patients harbored LPL variants on both alleles and presented with complete or severe LPL deficiency. The entire coding regions and splice junctions of LPL and four other TG metabolism genes (APOC2, APOA5, GPIHBP1, and LMF1) were analyzed by Sanger sequencing in a Han Chinese patient who had experienced two episodes of HTG-APIP. The impact of a novel LPL missense variant on LPL protein expression and activity was analyzed by transient expression in HEK293T cells. A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient. This variant did not affect protein synthesis but significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein. This report describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG-APIP. Our findings confirm a major genetic contribution to the etiology of individual predisposition to HTG-APIP. Show less

Hypertension is a complex disease that partially influenced by genetic factors. Up till now, the association between the rs651821 in apolipoprotein A5 (APOA5) gene and hypertension remains unknown. This study was undertaken to investigate the relationship between the APOA5 rs651821 and hypertension in Tongdao Dong population. A total of 274 participants were involved in this study (135 hypertensive patients and 139 nonhypertensive adults). The single nucleotide polymorphism (SNP) was genotyped by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The results showed that the genotypic and allelic frequencies of rs651821 were significantly different between the normotensives and hypertensive subjects ( Show less

Non-alcoholic fatty liver disease and obesity have interconnected genes, but it can also occur in non-obese population with body mass index < 25 kg/m(2). Non-obese type of non-alcoholic fatty liver disease mostly occurs in Asia. There is no significant difference between obese and non-obese type of non-alcoholic fatty liver in histological examination of liver biopsies. Visceral obesity, high fructose and cholesterol intake, and genetic factors such as APOC3 gene mutation are closely related to non-obese type of non-alcoholic fatty liver. Generally speaking, non-alcoholic steatohepatitis has an increased mortality rate, mainly due to cardiovascular causes, and has no link with other metabolic factors. Although data on the impact of mortality from non-obese type of non-alcoholic fatty liver disease are incomplete and limited, however diagnosis, management, and treatment may be important. Lifestyle changes to reduce visceral obesity, including dietary changes and physical activity, remain the main treatment options for patients with non-obese type of non-alcoholic fatty liver disease. Show less

Thyroid hormone is crucial for regulating lipid and glucose metabolism, which plays essential role in maintaining the health of pregnant women and their offspring. However, the current literature is just focusing on the development of offspring born to the untreated mothers with hypothyroidism, rather than mothers themselves. Additionally, the interaction between hypothyroidism and pregnancy, and its impact on the women's health are still elusive. Therefore, this study was designed to compare the metabolic differences in dams with hypothyroidism starting before pregnancy and after pregnancy. Pre-pregnant hypothyroidism was generated in 5-week-old female C57/BL/6J mice using iodine-deficient diet containing 0.15% propylthiouracil for 4 weeks, and the hypothyroidism was maintained until delivery. Gestational hypothyroidism was induced in dams after mating, using the same diet intervention until delivery. Compared with normal control, gestational hypothyroidism exhibited more prominent increase than pre-pregnant hypothyroidism in plasma total cholesterol and low-density lipoprotein cholesterol, and caused hepatic triglycerides accumulation. Similarly, more significant elevations of protein expressions of SREBP1c and p-ACL, while more dramatic inhibition of CPT1A and LDL-R levels were also observed in murine livers with gestational hypothyroidism than those with pre-pregnant hypothyroidism. Moreover, the murine hepatic levels of total cholesterol and gluconeogenesis were dramatically and equally enhanced in two hypothyroid groups, while plasma triglycerides and protein expressions of p-AKT, p-FoxO1 and APOC3 were reduced substantially in two hypothyroid groups. Taken together, our current study illuminated that gestational hypothyroidism may elicit more pronounced lipid dysregulation in dams than dose the pre-pregnant hypothyroidism. Show less

Dysregulation of the Wnt/β-catenin signaling pathway is involved in the development of human hepatocellular carcinoma and has thus emerged as a therapeutic target for this malignant tumor. In this study, we employed sensitive cell-based assays to identify aplykurodin A isolated from Show less

The dysregulation of ubiquitin ligase is the cause of many human diseases. Tripartite motif protein 32 (TRIM32) is an E3 ubiquitin ligase whose role in nucleus pulposus (NP) cell apoptosis is unclear. The expression of TRIM family protein and β-catenin in 40 NP tissue samples was detected by RT-PCR. Interleukin (IL)-1β or tumor necrosis factor (TNF)-α was used to treat rat NP cells. Knockdown and overexpression of Show less

Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies worldwide and has high morbidity and mortality. Elucidating the molecular mechanisms underlying HCC recurrence and metastasis is critical to identify new therapeutic targets. This study aimed to determine the roles of aminopeptidase N (APN, also known as CD13) in HCC proliferation and metastasis and its underlying mechanisms. We detected APN expression in clinical samples and HCC cell lines using immunohistochemistry, flow cytometry, real-time PCR, and enzyme activity assays. The effects of APN on HCC metastasis and proliferation were verified in both in vitro and in vivo models. RNA-seq, phosphoproteomic, western blot, point mutation, co-immunoprecipitation, and proximity ligation assays were performed to reveal the potential mechanisms. We found that APN was frequently upregulated in HCC tumor tissues and high-metastatic cell lines. Knockout of APN inhibited HCC cell metastasis and proliferation in vitro and in vivo. Functional studies suggested that a loss of APN impedes the ERK signaling pathway in HCC cells. Mechanistically, we found that APN might mediate the phosphorylation at serine 31 of BCKDK (BCKDK Show less

The Chromobox (CBX) protein family, which is a crucial part of the epigenetic regulatory complex, plays an important role in the occurrence and development of cancer; however, the function and prognostic value of CBX family members in gastric cancer is not clear. we investigated the relationship between CBX members and gastric cancer using a range of tools and databases: Oncomine, Kaplan-Meier plotter, cBioPortal, ULCAN, Metascape, and GEPIA. The results showed that, relative to normal gastric tissue, mRNA expression levels of CBX1-6 were significantly higher in gastric cancer tissue, whereas the level of CBX7 was significantly lower. Furthermore, overexpression of CBX3-6 and underexpression of CBX7 mRNAs was significantly related to the poor prognosis and survival of gastric cancer patients, making these CBX family members useful biomarkers. Finally, overexpression of CBX1 mRNA was significantly related to the poor prognosis of gastric cancer patients treated with adjuvant 5-fluorouracil-based chemotherapy. The members of the CBX family can be used as prognosis and survival biomarkers for gastric cancer and CBX1 may be a biomarker for choosing the chemotherapy regimen of gastric cancer patients. Show less