N6-methyladenosine reader protein IGF2BP1 suppresses CD8 + T cells-mediated tumor cytotoxicity and apoptosis in colon cancer.

Tumor immune escape is an important manner for colon cancer to escape effective killing by immune system. Currently, the immune checkpoint PD-1/PD-L1-targeted immunotherapy has emerged as a promising therapeutic strategy in colon cancer. Here, present work aims to investigate the biological function of N6-methyladenosine (m6A) reader insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) in regulating colon cancer's immune escape and CD8 + T cells-mediated tumor cytotoxicity and apoptosis. Results illustrated that IGF2BP1 was closely correlated to the colon cancer patients' poor clinical outcome. Functionally, upregulation of IGF2BP1 suppressed the CD8+ T-cells mediated antitumor immunity through reducing their tumor cytotoxicity. Mechanistically, MeRIP-Seq revealed that programmed death ligand 1 (PD-L1) mRNA had a remarkable m6A modified site on 3'-UTR genomic. Moreover, PD-L1 acted as the target of IGF2BP1, which enhanced the stability of PD-L1 mRNA. Overall, these results indicated that IGF2BP1 targeted PD-L1 to accelerate the immune escape in colon cancer by reducing CD8 + T cells-mediated tumor cytotoxicity in m6A-dependent manner. The findings demonstrate the potential of m6A-targeted immune checkpoint blockade in colon cancer, providing a novel insight for colon cancer immune escape and antitumor immunity in further precise treatment.

Populational genomic insights of Paraclostridium bifermentans as an emerging human pathogen.

Paraclostridium bifermentans (P.b) is an emerging human pathogen that is phylogenomically close to Paeniclostridium sordellii (P.s), while their populational genomic features and virulence capacity remain understudied. Here, we performed comparative genomic analyses of P.b and compared their pan-genomic features and virulence coding profiles to those of P.s. Our results revealed that P.b has a more plastic pangenome, a larger genome size, and a higher GC content than P.s. Interestingly, the P.b and P.s share similar core-genomic functions, but P.b encodes more functions in nutrient metabolism and energy conversion and fewer functions in host defense in their accessory-genomes. The P.b may initiate extracellular infection processes similar to those of P.s and Clostridium perfringens by encoding three toxin homologs (i.e., microbial collagenase, thiol-activated cytolysin, phospholipase C, which are involved in extracellular matrices degradation and membrane damaging) in their core-genomes. However, P.b is less toxic than the P.s by encoding fewer secretion toxins in the core-genome and fewer lethal toxins in the accessory-genome. Notably, P.b carries more toxins genes in their accessory-genomes, particularly those of plasmid origin. Moreover, three within-species and highly conserved plasmid groups, encoding virulence, gene acquisition, and adaptation, were carried by 25-33% of P.b strains and clustered by isolation source rather than geography. This study characterized the pan-genomic virulence features of P.b for the first time, and revealed that P. bifermentans is an emerging pathogen that can threaten human health in many aspects, emphasizing the importance of phenotypic and genomic characterizations of in situ clinical isolates.

Association between leptin receptor polymorphisms and polycystic ovary syndrome risk: a meta-analysis based on 11 studies.

OBJECTIVE: Published evidence indicated that the leptin receptor (LEPR) gene polymorphisms are associated with polycystic ovary syndrome (PCOS) risk. However, studies on the association between the polymorphisms of LEPR gene are inconsistent or even controversial. MATERIAL AND METHODS: We conducted this meta-analysis to explore the more precise relationship between LEPR polymorphisms and PCOS risk. Relevant articles were searched with five online databases up to March 1 2023. Odds ratios (OR) with 95% confidence intervals (CI) were selected to examine the statistical strength of each genetic model. Moreover, RNA secondary structure and variant effects of these loci were examined with in silico analysis. RESULTS: Overall, 11 publications were analyzed, and the pooled results did not present any significant association between rs1137101 A/G polymorphism and PCOS risk in general population and some subgroup analysis. But the significant association were observed in Asian population (AG vs. AA: OR = 0.51, 95%CI = 0.32-0.81, p = .01, I2=0%; AG + GG vs. AA: OR = 0.41, 95%CI = 0.26-0.65, p < .01, I2=25.9%). Moreover, similar positive associations were also observed in rs1805096 polymorphism with PCOS risk. CONCLUSION: In summary, our meta-analysis suggested that the LEPR gene polymorphisms might be associated with PCOS susceptibility. Owing to the limited studies and small sample size in our meta-analysis, more well-designed studies from different races were needed to be conducted to verify the current results.

No association between myeloperoxidase gene rs2333227 G>A polymorphism and Alzheimer's disease risk: a meta-analysis and trial sequential analysis.

Evidence suggests that there is a close association between myeloperoxidase (MPO) gene rs2333227 G>A polymorphism with Alzheimer's disease (AD) susceptibility. We conducted a meta-analysis to explore the precise association between MPO rs2333227 G>A polymorphism and AD susceptibility. Online databases were searched and the relevant information was collected. Crudeodds ratios with 95% confidence intervals were calculated. Trial sequential analysis (TSA), heterogeneity analyses, accumulative analyses, sensitivity analyses, and publication biasestests were performed. Overall, nine publications (ten independent case-controls) were included in this meta-analysis, involving 3260 participants. Pooled results revealed no significant association between MPO rs2333227 G>A polymorphism and AD susceptibility was observed. TSA showed that the present meta-analysis remained inconclusive due to insufficient evidence. In summary, the current meta-analysis indicated that the MPO rs2333227 G>A polymorphism may not be acausalfactor in the development of AD.

Association Between Angiotensin-Converting Enzyme Gene I/D Polymorphism and Polycystic Ovary Syndrome Susceptibility: a Meta-analysis.

Rec ent studies have suggested a closer association between angiotensin-converting enzyme (ACE) gene polymorphisms and polycystic ovary syndrome (PCOS) risk, but the results were inconsistent. We conducted this meta-analysis to explore the precise associations between ACE gene I/D polymorphism and PCOS risk. Online electronic databases (PubMed, Embase, SCI index, CNKI, and Wanfang) were searched. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated to assess the association between ACE gene I/D polymorphism and PCOS risk. In addition, heterogeneity, accumulative/sensitivity analysis, and publication bias were conducted to check the statistical power. Overall, 12 published case-control studies with 2248 patients and 1759 controls were included according to the criteria. Significant increased risk was found for PCOS susceptibility with I/D mutation (D vs. I: OR = 1.62, 95%CI = 1.24-2.11, P < 0.01, I2 = 86.1%; DD vs. II: OR = 2.10, 95%CI = 1.35-3.27, P < 0.01, I2 = 79.8%; ID + DD vs. II: OR = 1.57, 95%CI = 1.06-2.32, P = 0.02, I2 = 79.3%; DD vs. II + ID: OR = 1.91, 95%CI = 1.39-2.65, P < 0.01, I2 = 79.1%). Furthermore, some similar associations were also observed in subgroups. In summary, the current evidences indicated that ACE gene I/D polymorphism plays an important role in PCOS development, both in Asian and Caucasian descendants.

Relationship between PPAR-γ gene polymorphisms and ischemic stroke risk: A meta-analysis.

BACKGROUND: Published researches have suggested some associations between PPAR-γ and ischemic stroke (IS) development. This meta-analysis was conducted to evaluate the association between PPAR-γ gene polymorphisms and IS risk. MATERIALS AND METHODS: A systematic search was conducted in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang databases. The pooled association of odd ratios (ORs) and its 95% confidence interval (CI) was calculated to assess the IS risk of PPAR-γ rs1801282 C/G and rs3856806 C/T polymorphisms. Furthermore, the heterogeneity test, cumulative analyses, sensitivity analyses, and publication bias were conducted. RESULT: Sixteen publications with 3786 cases and 5343 controls were identified. Overall findings indicated that rs1801282 C/G polymorphism may be associated with an increased risk for IS (GG vs. CC: OR = 2.17 95%CI = 1.09-4.35, p = .03, I2  = 0%; GG vs. CC+CG: OR = 2.15, 95%CI = 1.07-4.32, p = .03, I2  = 0%). The similar results were also found in the subgroup analysis. In addition, no significant association was observed between rs3856806 C/T polymorphism and IS risk. CONCLUSION: In conclusion, our study showed that PPAR-γ rs1801282 C/G polymorphism probably plays an important role in IS occurrence. The result should be verified with more studies in the future.

Association Between the Aldehyde Dehydrogenase-2 rs671 G>A Polymorphism and Head and Neck Cancer Susceptibility: A Meta-Analysis in East Asians.

BACKGROUND: Aldehyde dehydrogenase-2 (ALDH2) plays an important role in the alcohol detoxification and acetaldehyde metabolism. Published studies have demonstrated some inconsistent associations between ALDH2 rs671 G>A polymorphism and head and neck cancer (HNC) risk. METHODS: A meta-analysis was performed to provide pooled data on the association between the ALDH2 rs671 G>A polymorphism and HNC risk. Electronic databases were searched to identify relevant studies. Odds ratios and 95% confidence intervals (CIs) were used to examine the pooled effect size of each genetic model. In addition, heterogeneity test, accumulative analysis, sensitivity analysis, and publication bias were conducted to test the statistical power. RESULTS: Thirteen publications (14 independent case-control studies) involving 10,939 subjects were selected. The stratified analysis indicated that both light/moderated drinking (e.g., GA vs. GG: OR = 1.47, 95% CI = 1.16 to 1.86, p < 0.01, I2  = 81.1%) and heavy drinking would increase HNC risk with rs671 G>A mutation (e.g., GA vs. GG: OR = 2.30, 95% CI = 1.11 to 4.77, p = 0.03, I2  = 81.9%). CONCLUSIONS: In summary, this meta-analysis suggested that the ALDH2 rs671 G>A polymorphism may play an important synergistic effect in the pathogenesis of HNC development in East Asians.

Serum pepsinogen assay is not recommended for the diagnosis of esophageal squamous cell carcinoma: a systematic review and meta-analysis.

Background: Serum pepsinogen I (PGI) concentration and PGI/PGII ratio (PGR) are often used as serological markers for gastric fundus atrophy (AGA) and gastric carcinoma. However, their diagnostic value in esophageal carcinoma (EC) is inaccurate. Methods: This study evaluated the diagnostic value of PGI and PGR in EC by searching the PubMed, Web of Science, Embase, Cochrane Library and Cochrane Central Register of Controlled Trials databases for literature on the diagnosis of EC with PGI and PGR from January 1, 2000 to October 2, 2018. The included literature were systematically evaluated using QUSDAS-2 software. Meta-analysis was conducted using STATA 15.0 software. The summary receiver operating characteristic curve (SROC) accuracy was plotted, the area under the curve was calculated. Results: A total of 84 papers were selected, and after screening, nine papers on esophageal squamous cell carcinoma (ESCC) were finally included. Results showed low an ESCC-specific diagnostic sensitivity (0.27), high specificity (0.85), and 0.63 AUC of SROC when PGI≤70 ng/mL. When PGR≤3, the ESCC-specific diagnostic sensitivity was low (0.29), the specificity was high (0.83), and the AUC of SROC was 0.63. Conclusion: According to the current research results, PGI≤70 ng/mL or PGR≤3 diagnostic ESCC sensitivity is low, and specificity is high. These findings indicate that neither PGI≤70 ng/mL nor PGR≤3 can be used as an ESCC-screening index.

ZFAS1 knockdown inhibits viability and enhances cisplatin cytotoxicity by up-regulating miR-432-5p in glioma cells.

BACKGROUND: Long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) is a novel vital oncogenic lncRNA that is dysregulated in various types of cancers, including glioma. According to TargetScan prediction, miR-432-5p is a target of ZFAS1. Herein, we aimed to determine whether there was a correlation between ZFAS1 and miR-432-5p and to explore their roles in glioma. METHODS: The expression levels of ZFAS1 and microRNA (miR)-432-5p in clinical tissues and cell lines were measured using RT-qPCR. Cell viability was detected using MTT assay. Cell apoptosis was examined using flow cytometry. The association between ZFAS1 and miR-432-5p was confirmed using luciferase reporter and RNA pull-down assays. RESULTS: Zinc finger antisense 1 expression was up-regulated, while miR-432-5p expression was down-regulated in both glioma tissues and cells. Knockdown of ZFAS1 and miR-432-5p overexpression inhibited cell viability and enhanced the chemosensitivity of glioma cells to cisplatin. MiR-432-5p was a direct target of ZFAS1 in glioma cells. Inhibition of miR-432-5p blocked the effects of ZFAS1 knockdown on cell viability and cisplatin sensitivity. CONCLUSIONS: Knockdown of ZFAS1 inhibited the viability and enhanced cisplatin sensitivity via targeting miR-432-5p in glioma cells.

Neuroprotective Influence of miR-301a Inhibition in Experimental Cerebral Ischemia/Reperfusion Rat Models Through Targeting NDRG2.

The objective of this study is to find out the potential influence of miR-301a in an experimental cerebral ischemia-reperfusion (I/R) rat model through targeting NDRG2. Rats with cerebral I/R injury were constructed and classified into model, miR-301a inhibitor, miR-301a mimic, NC (negative control), siNDRG2, NDRG2, and miR-301a inhibitor + si-NDRG2 groups, as well as another sham group. Cerebral infarct volume and cell apoptosis were observed by TTC staining and TUNEL staining. The targeting relationship between miR-301a and NDRG2 was verified by luciferase assay. ELISA, qRT-PCR, and Western blot were used to detect the expressions of related molecules. Compared with sham group, rats in the model group had elevated neurological function score and infarct volume; meanwhile, the cell apoptosis rate and inflammatory response were also increased with enhanced expression of miR-301a and NDRG2 (all P < 0.05). These changes were worsened in the miR-301a mimic and si-NDRG2 groups. Conversely, those rats in the miR-301a inhibitor and NDRG2 groups presented increased NDRG2, and at the same time, other above concerning factors also exhibited opposite tendencies (all P < 0.05). Dual-luciferase reporter gene assay confirmed that NDRG2 was a target gene of miR-301a, and si-NDRG2 could reverse the neuroprotective effect of miR-301a inhibitor in rats with cerebral I/R injury. Inhibiting miR-301a has a neuroprotective effect on rats with cerebral I/R injury to ameliorate cell apoptosis and inflammatory response through possibly targeting NDRG2.

Combined detection of IL-6 and IL-8 is beneficial to the diagnosis of early stage esophageal squamous cell cancer: a preliminary study based on the screening of serum markers using protein chips.

BACKGROUND: The diagnosis rate of early stage esophageal squamous cell carcinoma (ESCC) is low due to the lack of specific tumor markers. Seeking for these markers is beneficial to improve the early diagnosis rate and the prognosis of patients. This study profiles the differentially expressed proteins of early stage ESCC patients via the AAH-BLG-507 protein chip, which further consolidates the clinical evidence of ESCC diagnosis. MATERIALS AND METHODS: In this study, 20 serum samples were collected from Taihe Hospital between August 2016 and June 2017. Ten of them carried ESCC, while the rest were healthy controls. To profile the proteins' expression level, the AAH-BLG-507 protein chip was used, and both highly expressed and lowly expressed proteins were fished out. Meanwhile, their biological roles were examined by using Gene Ontology (GO) database and String database, and they were further verified by ELISA. RESULTS: Results showed that the expression levels of AXL, ARTN, Ang2, BDNF, BMP7, cripto-1, CCL28, E-selectin, IL-6, IL-8 and SHH in the serum of early ESCC were significantly upregulated (P<0.05), particularly IL-6 and IL-8. The expression levels of TSP1 and MMP-8 were markedly downregulated (P<0.05). Analysis showed that these proteins were mainly involved in angiogenesis, signal transduction, cell proliferation and migration, indicating the close relationship with the development of ESCC. CONCLUSION: It suggested that IL-6 and IL-8 proteins could be considered as the markers for ESCC diagnosis.

Effectiveness and Tolerability of Different Recommended Doses of PPIs and H2RAs in GERD: Network Meta-Analysis and GRADE system.

Proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are used for gastro-esophageal reflux disease (GERD); however, the clinical evidence for treatment is poor. We evaluated the effectiveness and tolerability of different doses of PPIs, H2RAs and placebo in adults with GERD. Six online databases were searched through September 1, 2016. All related articles were included and combined with a Bayesian network meta-analysis from randomized controlled trials (RCTs). The GRADE systems were employed to assess the main outcome. Ninety-eight RCTs were identified, which included 45,964 participants. Our analysis indicated that the full/standard dose of esomeprazole at 40 mg per day was the most efficient in healing among nine different dosages of PPIs and H2RAs. The main efficacy outcome did not change after adjustments for the area, age, level of disease from endoscopy, year of publication, pharmaceutical industry sponsorship, Intention-to-treat (ITT)/per-protocol (PP), withdrawal rate, pre-set select design bias, single blinded and unblinded studies, study origination in China, study arms that included zero events, inconsistency node or discontinued drug were accounted for in the meta-regressions and sensitivity analyses. This research suggests that the full/standard doses (40 mg per day) of esomeprazole should be recommended as first-line treatments for GERD in adults for short-term therapy.

CCND1 G870A polymorphism and colorectal cancer risk: An updated meta-analysis.

Molecular epidemiological studies have revealed a closer association between cyclin D1 (CCND1) polymorphism and the risk of colorectal cancer; however, the results were inconsistent. The aim of the present meta-analysis was to investigate the association between CCND1 G870A polymorphism and colorectal cancer risk. Online electronic databases (PubMed and Embase) were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between CCND1 G870A polymorphism and the risk of colorectal cancer. In addition, heterogeneity, publication bias and sensitivity analysis were performed to guarantee the statistical power. In total, 23 published case-control studies with 6,320 patients and 8,252 controls were selected. Significantly increased risks were observed in four genetic models (A vs. G: OR=1.09, 95% CI=1.00-1.18, I2=54.3%; GA vs. GG: OR=1.13, 95% CI=1.04-1.24, I2=18.2%; AA vs. GG, OR=1.17: 95% CI=1.00-1.38, I2=52.5%; GA+AA vs. GG: OR=1.14, 95% CI=1.05-1.24, I2=33.8%). Similarly, significant associations were also identified in the stratified analysis in the cancer subtype of sporadic colorectal cancer (GA vs. GG: OR=1.21, 95% CI=1.04-1.42, I2=24.1%; GA+AA vs. GG: OR=1.18, 95% CI=1.02-1.37, I2=35.0%), Caucasian population (GA vs. GG, OR=1.14, 95% CI=1.02-1.28, I2=19.8%; GA+AA vs. GG, OR=1.14, 95% CI=1.02-1.27, I2=37.5%) and other subgroups of control design and genotyping type. The present updated meta-analysis suggested that CCND1 G870A may present an increased risk for developing colorectal cancer, particularly in sporadic colorectal cancer and a Caucasian population.

Clinical implications of PTEN and VEGF expression status, as well as microvessel density in esophageal squamous cell carcinoma.

There are limitations to the use of single biomarker levels, for example phosphate and tensin homology (PTEN) or vascular endothelial growth factor (VEGF), in the diagnosis of esophageal squamous cell carcinoma (ESCC). The present study therefore aimed to evaluate the clinical implications of combined detection of multiple biomarkers. The associations between PTEN and VEGF expression status, microvessel density (MVD), and the pathological characteristics of 50 patients with ESCC were determined using χ2, analysis of variance, and t-tests. The results indicated that the PTEN-positive rate was negatively correlated with ESCC histological grade (P<0.01), depth of ESCC invasion (P<0.01) and lymph node metastasis status. Furthermore, the VEGF-positive rate was correlated with lymph node metastasis status, while MVD was correlated with the depth of ESCC invasion (P<0.01) and lymph node metastasis status (P<0.05). The PTEN-positive rate was negatively correlated with the VEGF-positive rate. A higher MVD was identified in ESCC samples than that of the normal esophageal mucosa, particularly in VEGF-positive ESCC specimens compared with those of VEGF-negative specimens, and PTEN-negative ESCC specimens compared with that of the PTEN-positive ESCC specimens. These results suggested that combined detection of PTEN and VEGF levels, as well as evaluation of MVD in patients with ESCC may provide essential information for improvements in the diagnosis and prognosis of ESCC.

Association of interleukin-17 gene polymorphisms and Helicobacter pylori infection with gastric cancer susceptibility: a cumulative and comprehensive meta-analysis.

BACKGROUND: The association between Interleukin-17(IL-17) gene polymorphisms and Helicobacter pylori (H. pylori) infection and gastric cancer susceptibility were inconsistent. We therefore performed a comprehensive meta-analysis about all three genetic polymorphisms of IL-17 to derive a more precise estimation. METHODS: PubMed, Embase, CNKI and Wanfang databases were researched on the associations between IL-17A rs2275913G>A, rs3748067C>T and IL-17F rs763780 T>C and gastric cancer risk. Odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the relationships. Publication bias, sensitivity and cumulative analysis was conducted to guarantee the strength of meta-analysis. RESULTS: Overall, eleven related studies involving 4,478 cases and 5,612 controls were collected. Significantly increased risk between IL-17A rs2275913G>A polymorphism and gastric cancer were observed (A vs. G: OR = 1.22, 95% CI = 1.08-1.37, P<0.01, I(2) = 72.3%; AA vs. GG: OR = 1.55, 95% CI = 1.21-1.99, P<0.01, I(2) = 74.3%; GA + AA vs. GG: OR = 1.19, 95% CI = 1.05-1.39, P<0.01, I(2) = 48.2%; AA vs. GG + GA: OR = 1.50, 95% CI = 1.16-1.95, P<0.01, I(2) = 81.2%). For IL-17F rs3748067C>T and rs763780 T>C polymorphisms, only few significantly increased risk could be found in genetic models. Moreover, H. pylori infection also be proved to increase the risk of gastric cancer combined with rs3748067C>T mutation. CONCLUSIONS: Our meta-analysis suggests that the three IL-17 polymorphisms were associated with a significantly increased risk of gastric cancer, especially in Chinese.

GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells.

AIM: To investigate the effect of GW4064 on the expression of adipokines and their receptors during differentiation of 3T3-L1 preadipocytes and in HepG2 cells. METHODS: The mRNA expression of farnesoid X receptor (FXR), peroxisome proliferator-activated receptor-gamma 2 (PPAR-γ2), adiponectin, leptin, resistin, adiponectin receptor 1 (AdipoR1), adiponectin receptor 2 (AdipoR2), and the long isoform of leptin receptor (OB-Rb) and protein levels of adiponectin, leptin, and resistin were determined using fluorescent real-time PCR and enzyme linked immunosorbent assay, respectively, on days 0, 2, 4, 6, and 8 during the differentiation of 3T3-L1 preadipocytes exposed to GW4064. Moreover, mRNA expression of AdipoR2 and OB-Rb was also examined using fluorescent real-time PCR at 0, 12, 24, and 48 h in HepG2 cells treated with GW4064. RESULTS: The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, resistin, AdipoR1, AdipoR2, and OB-Rb and protein levels of adiponectin, leptin, and resistin increased along with differentiation of 3T3-L1 preadipocytes (P < 0.05 for all). The mRNA expression of FXR, PPAR-γ2, adiponectin, leptin, and AdipoR2 in 3T3-L1 preadipocytes, and AdipoR2 and OB-Rb in HepG2 cells was significantly increased after treatment with GW4064, when compared with the control group (P < 0.05 for all). A similar trend was observed for protein levels of adipokines (including adiponectin, leptin and resistin). However, the expression of resistin, AdipoR1, and OB-Rb in 3T3-L1 cells did not change after treatment with GW4064. CONCLUSION: The FXR agonist through regulating, at least partially, the expression of adipokines and their receptors could offer an innovative way for counteracting the progress of metabolic diseases such as nonalcoholic fatty liver disease.

ZNF703 promotes tumor cell proliferation and invasion and predicts poor prognosis in patients with colorectal cancer.

Zinc finger protein 703 (ZNF703), identified as an oncogene in luminal B breast cancer, is a member of the NET/NlZ family of zinc finger transcription factors. However, the role of ZNF703 in colorectal cancer (CRC) is unknown. We investigated the expression of ZNF703 in paired tumor and corresponding normal tissues using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. Immunohistochemistry (IHC) was applied on paraffin-embedded specimens, including 138 CRC tissues, 58 matched normal tissues and 30 paired metastatic lymph node samples. Levels of mRNA (72.72%, 16/22) and ZNF703 protein expression (65.38%, 17/26, respectively) were upregulated in CRC tissues. IHC staining revealed higher expression of ZNF703 in the CRC tissues (68/138, 49.3%) compared with that in the adjacent normal mucosal tissues (4/58, 6.9%) (p<0.001). Moreover, high ZNF703 expression was significantly correlated with tumor size, pathological grading, serosal invasion, lymph node metastasis and AJCC stage. CRC patients with relatively low ZNF703 expression had higher survival rates than those with high ZNF703 expression. In addition, we investigated ZNF703 expression in eight CRC cell lines (LS174T, SW480, HT29, SW620, DLD1, SW1116, LoVo and CaCo-2) in vitro. The highest ZNF703 expression was detected in the LoVo cell line. RNA interference was used to assess the effects of ZNF703 knockdown in LoVo cells. Knockdown of ZNF703 expression inhibited CRC cell proliferation and migration. Collectively, these results reveal that ZNF703 may act as an oncogene in CRC and could be considered as a potential therapeutic target for metastatic CRC.

CCND1 G870A polymorphism contributes to the risk of esophageal cancer: An updated systematic review and cumulative meta-analysis.

The common functional cyclin D1 (CCND1) G870A polymorphism may influence the risk of esophageal cancer. However, the conclusions of previous studies have been inconsistent for the association between the CCND1 G870A polymorphism and esophageal cancer risk. A meta-analysis of 11 published case-control studies was performed, including 2,111 patients with esophageal cancer and 3,232 controls, to investigate the association between the CCND1 G870A polymorphism and esophageal cancer risk. The odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between the CCND1 G870A polymorphism and esophageal cancer risk. A significant association between the CCND1 G870A polymorphism and esophageal cancer risk was observed for the allele contrast (A vs. G: OR, 1.23; 95% CI, 1.02-1.48; P=0.029), codominant (AA vs. GG: OR, 1.58; 95% CI; 1.06-2.35; P=0.024) and recessive models (AA vs. GG + GA: OR, 1.33, 95% CI, 1.03-1.73; P=0.030). However, in the stratified analysis by ethnicity, study design and pathology, there was no significant association detected in these genetic models. In conclusion, results of the meta-analysis suggested that the CCND1 G870A polymorphism is a potential risk factor in the development of esophageal cancer.

ZNF703 acts as an oncogene that promotes progression in gastric cancer.

ZNF703, a member of the NET/Nlz family of zinc finger transcription factors, contributes to aspects of developmental growth and patterning across evolutionarily diverse species. ZNF703 has been identified as a novel oncogene in human breast cancer. In the present study, we investigated the expression of ZNF703 in gastric carcinoma and attempted to determine, using cell line models, its biological actions. Using immunohistochemistry, we analyzed the ZNF703 protein expression in 120 clinicopathologically characterized gastric cancer cases. Using RNA interference, we investigated the effects of ZNF703 depletion on tumor proliferation and metastasis in vitro. We found that ZNF703 was overexpressed in invasive gastric carcinoma tissues, and its expression levels were closely correlated with the depth of invasion, node metastasis and venous invasion. RNA interference-mediated silencing of the ZNF703 gene in SGC7901 cells inhibited cell proliferation and migration significantly. The results showed that ZNF703 acts as a gastric cancer oncogene and should be considered a therapeutic target for metastatic gastric cancer.

Interleukin-11 induces the expression of matrix metalloproteinase 13 in gastric cancer SCH cells partly via the PI3K-AKT and JAK-STAT3 pathways.

Interleukin (IL)-11 is expressed in the majority of gastric carcinomas and has been associated with an aggressive phenotype and poor prognosis of gastric adenocarcinoma. Matrix metalloproteinase (MMP)-13 has been detected in numerous invasive malignant tumor types and exhibits a broad spectrum of activities on connective tissue components. In this study, we investigated whether IL-11 affects the expression of MMP-13 in human gastric cancer cells, as well as the underlying mechanism. Using western blot assays, we investigated the effect of recombinant human (rh) IL-11 on the expression of MMP-13 in gastric carcinoma cell lines. Using the PI3K inhibitor wortmannin and RNA interference to target the STAT3 gene, we investigated the effects of PI3K inhibition and/or STAT3 depletion on the expression of the MMP-13 protein. Results showed that IL-11 induced MMP-13 expression in a time- and concentration-dependent manner in SCH cells. IL-11 activated PI3K-AKT and JAK-STAT3 signal transduction. Wortmannin and depletion of STAT3 by means of small interfering RNA (siRNA) synergistically reduced the expression of MMP-13. These findings suggested that IL-11 induces the expression of MMP-13 in gastric cancer SCH cells partly via the PI3K-AKT and JAK-STAT3 pathways.