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Oxidative stress-induced autophagy helps to prevent cellular damage and to maintain homeostasis. However, the regulatory pathway that initiates autophagy remains unclear. We previously showed that reactive oxygen species (ROS) function as signaling molecules to activate the ATM-CHK2 pathway and promote autophagy. Here, we find that the E3 ubiquitin ligase TRIM32 functions downstream of ATM-CHK2 to regulate ATG7 ubiquitination. Under metabolic stress, ROS induce ATM phosphorylation at S1981, which in turn phosphorylates CHK2 at T68. We show that CHK2 binds and phosphorylates TRIM32 at the S55 site, which then mediates K63-linked ubiquitination of ATG7 at the K45 site to initiate autophagy. In addition, Chk2 −/− mice show an aggravated infarction phenotype and reduced phosphorylation of TRIM32 and ubiquitination of ATG7 in a stroke model. We propose a molecular mechanism for autophagy initiation by ROS via the ATM-CHK2-TRIM32-ATG7 axis to maintain intracellular homeostasis and to protect cells exposed to pathological conditions from stress-induced tissue damage. [Display omitted] • TRIM32 mediates ATG7 K63-linked ubiquitination, which initiates autophagy • ROS-ATM-CHK2 signaling pathway regulates ATG7 ubiquitination via phosphorylation of TRIM32 • ATM-CHK2-TRIM32-ATG7 signaling pathway is a protective mechanism against oxidative stress Liu et al. elucidate the molecular mechanism involved in the activation of ATM-CHK2-TRIM32-ATG7 axis by ROS under metabolic stress. ATM-CHK2-TRIM32-ATG7 axis is a phosphorylation-ubiquitination cascade that activates autophagy as a physiological adaptation pathway that can protect cells exposed to pathological conditions from stress-induced tissue damage. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin, they have been increasingly shown to have aberrant expression in many tumor types. miR-203 has not been comprehensively investigated in gastric and colorectal cancers.Methods: Total RNA was extracted from tissues of 212 patients with gastric or colorectal cancer as well as from seven gastric and colorectal cell lines. We determined the expression of miR-203 by real-time PCR and calculated using the 2-ΔΔCt method. Then, we assessed miR-203 expression and clinicopathologic characteristics. Finally, we studied the effect of miR-203 on cell proliferation in SGC-7901 cells by MTT.Results: miR-203 has significantly low expression in colorectal cancer tissues (p < 0.001, paired t test) and cancer cell lines compared to non-tumor counterparts. Moreover, low expression of miR-203 was correlated with tumor size (p = 0.015, non-parametric test) and pT stage (p = 0.005) in colorectal cancer. Although expression of miR-203 was not significant in gastric cancer tissues (p = 0.124), interestingly, miR-203 was correlated with tumor size (p = 0.023), macroscopic type (p = 0.045), and pT stage (p = 0.013). Furthermore, we found miR-203 can inhibit the cell proliferation in SGC-7901 cells.Conclusion: miR-203 may be related to the proliferation and invasion of gastric and colorectal cancers. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs are endogenous small noncoding RNAs that aberrantly expressed in various carcinomas. MiR-148a and miR-152, which have the same "seed region", have not been comprehensively investigated in gastrointestinal cancers.Methods: Total RNA was extracted from the tissues of 101 patients with gastric cancer and 101 patients with colorectal cancer as well as their matched nontumor adjacent tissues. After polyadenylation and reverse transcription, the expression of miR-148a and miR-152 was determined using quantitative real-time polymerase chain reaction. The protein level of cholecystokinin B receptor, which might be the target gene of miR-148a and miR-152, was analyzed by Western blot in 40 patients with gastric cancer.Results: Expression levels of miR-148a and miR-152 in human gastric (p < 0.001 and p = 0.038, respectively, t-test) and colorectal (all p < 0.001) cancers were significantly lower than that in their matched nontumor adjacent tissues. Moreover, their low expression was also found in several gastrointestinal cancer cell lines compared with normal gastric epithelial cell line and normal colorectal tissue, respectively. A strong correlation was found between the expression of miR-148a and miR-152 (all p < 0.001, Pearson's correlation). Furthermore, low expression of miR-152 was correlated with increased tumor size (p = 0.023 and 0.004, respectively, Mann-Whitney U test) and advanced pT stage (p = 0.018 and 0.002, respectively) in gastrointestinal cancers. Low expression of miR-148a was also correlated with increased tumor size (p = 0.045 and 0.018, respectively) in gastrointestinal cancers, but only correlated with advanced pT stage (p = 0.023) in colorectal cancer. We also found the expression of miR-148a (p < 0.001, chi-square test) and miR-152 (p = 0.002) inversely correlated with cholecystokinin B receptor protein in gastric cancer.Conclusion: MiR-148a and miR-152 may be involved in the carcinogenesis of gastrointestinal cancers and might be potential biomarkers in these cancers. [ABSTRACT FROM AUTHOR]

Human genomic DNA is in a dynamic balance of damage and repair. Cells employ multiple and specific repair pathways, such as nucleotide excision repair (NER), as unrepaired DNA damage has deleterious consequences and could give rise to carcinogenesis. Gene polymorphisms play a crucial role in predicting the risk and prognosis of cancer. Polymorphisms of NER-related genes could alter the ability of NER to effectively monitor and repair DNA damage, and thus may be associated with genetic susceptibility, chemotherapeutic sensitivity and prognosis of cancer. In recent years, increasing studies have focused on the association between polymorphisms of NER genes and gastric cancer, the world's fourth most common cancer and the second most common cause for cancer-related death. Here we reviewed the recent studies on the associations between polymorphisms of NER genes and gastric cancer from perspectives of genetic susceptibility, chemotherapeutic sensitivity and prognosis. [ABSTRACT FROM AUTHOR]

Background: Relatively little is known about preoperative anxiety and its associated factors with colorectal cancer, which is one of the most prevalent cancers. We aimed to investigate preoperative anxiety and its associated social, psychological and coping factors based on the disclosure/nondisclosure of cancer diagnosis.Methods: A cross-sectional study was conducted in consecutive colorectal cancer inpatients (N = 434), whose anxiety was assessed based on semi-structured interview, demographic-clinical variables, social support, self-esteem and coping styles (acceptance-resignation, confrontation, avoidance). Hierarchical regression analyses were conducted to explore the relationships between social, psychological, coping factors and preoperative anxiety.Results: There was no significant difference in preoperative anxiety (χ2 = 1.031, p = .31) between the disclosure and nondisclosure groups. Social, psychological and coping factors together accounted for an additional variance of preoperative anxiety (disclosure: 22%; nondisclosure: 20.8%). Social support (β = -0.17, p = .004), self-esteem (β = -0.22, p = .001) and coping styles (acceptance-resignation: β = 0.32, p < .001; confrontation: β = 0.13, p = .06; avoidance: β = -0.17, p = .04) were associated with preoperative anxiety in the nondisclosure group. For the disclosure group, acceptance-resignation was the only significantly associated factor of preoperative anxiety (β = 0.37, p < .001).Conclusions: Coping styles, such as acceptance-resignation and confrontation, could aggravate preoperative anxiety. Avoidance, social support and self-esteem might be helpful in preventing preoperative anxiety. These findings highlight the importance of providing psychological interventions for cancer patients by integrating social support, self-esteem and coping styles when disclosing a cancer diagnosis. [ABSTRACT FROM AUTHOR]

Increasing number of studies focused on the association of IL-17A rs2275913 and IL-17F rs763780 polymorphisms with gastric cancer (GC) risk. However, the results were inconsistent. To elucidate the exact association, we performed the present meta-analysis. Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched for potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to evaluate the strength of association. Eight studies for IL-17A rs2275913 (3345 cases and 4427 controls) and five studies for IL-17F rs763780 (1784 cases and 2592 controls) were finally included. The results indicated that individuals with AA genotype of IL-17A rs2275913 polymorphism were associated with increased GC risk compared with wild-type GG (OR = 1.61, 95% CI = 1.17–2.23, P = 0.004); A allele was significantly associated with increased GC risk compared with G allele (OR = 1.22, 95% CI = 1.06–1.41, P = 0.007). IL-17F rs763780 polymorphism was also significantly associated with increased GC risk (CC vs. CT: OR = 1.40, 95% CI = 1.04–1.88, P = 0.025; CT vs. TT: OR = 1.35, 95% CI = 1.16–1.58, P < 0.001; C allele vs. T allele: OR = 1.30, 95% CI = 1.15–1.47, P < 0.001). In summary, IL-17A rs2275913 A/G polymorphism and IL-17F rs763780 C/T polymorphism might be associated with increased GC risk in Asians. Further large-scale studies are still required to confirm the results of this meta-analysis. [ABSTRACT FROM AUTHOR]

Abstract: Genetic polymorphisms in excision repair cross-complementing group 4 (ERCC4) may contribute to the risk of cancer development. However, there are few reports regarding to susceptibility to gastric cancer (GC) or its precursor, atrophic gastritis (AG). Thereby, we investigated the association between two tag single nucleotide polymorphisms (tagSNPs) rs6498486 and rs254942, which represents the majority of common SNPs of ERCC4 gene, and the risks of GC and AG development in a sex- and age-matched case–control designed study. We found that rs6498486 polymorphism was associated with a reduced AG risk in total population (for AC vs. AA: OR=0.69, 95%CI=0.52–0.94, P=0.016; for AC/CC vs. AA: OR=0.68, 95%CI=0.51–0.92, P=0.010) as well as in the subpopulation of youngers (age<60years) (for AC/CC vs. AA: OR=0.67, 95%CI=0.45–0.99, P=0.048). For the rs254942 polymorphism, compared with the common TT genotype, the genotypes of CT and CT/CC were only observed to reduce AG risk in the subgroups of males (for CT vs. TT: OR=0.64, 95%CI=0.45–0.90, P=0.012; for CT/CC vs. TT: OR=0.66, 95%CI=0.47–0.92, P=0.016) and youngers (for CT vs. TT: OR=0.72, 95%CI=0.53–0.97, P=0.035; for CT/CC vs. TT: OR=0.74, 95%CI=0.55–0.99, P=0.045). However, no significant statistical association of the two SNPs with GC susceptibility was observed in the total population. Only rs6498486 AC and AC/CC genotypes were found to be marginally associated with a reduced GC risk in the subgroup of males (for AC vs. AA: OR=0.69, 95%CI=0.49–0.99, P=0.043; for AC/CC vs. AA: OR=0.71, 95%CI=0.50–0.99, P=0.046). Our findings suggested that the ERCC4 rs6498486 and rs254942 may be associated with AG risk. Further validation of our results in larger populations and additional studies evaluating their molecular function are required. [Copyright &y& Elsevier]

Abstract: Genetic variations in excision repair cross-complementing group 5 (ERCC5) might influence individual vulnerability to gastric cancer (GC). We investigated effects of two putatively functional polymorphisms in ERCC5 promoter region, rs751402 (+25A>G) and rs2296147 (+202C>T), and their potential interaction with environment factors on the risk of developing GC. We performed a sex- and age-matched case–control design with 400 GC cases and 400 healthy controls for rs751402 and 403 GC cases and 403 healthy controls for rs2296147. Our results showed that rs751402 were associated with increased GC risk (AA vs. GG: OR=1.99, 95%CI: 1.20–3.31, P=0.008; AG+AA vs. GG: OR=1.41, 95%CI: 1.07–1.86, P=0.016), and rs2296147 was also associated with increased cancer risk (CC vs. TT: OR=2.17, 95%CI: 1.04–4.54, P=0.039; CC vs. CT+TT: OR=2.26, 95%CI: 1.09–4.69, P=0.028). In a stratified analysis, rs751402 (AG+AA vs. GG: OR=1.44, 95%CI: 1.02–2.02, P=0.037) and rs2296147 (CC vs. CT+TT: OR=2.33, 95%CI: 1.00–5.44, P=0.050) were also found to be associated with diffuse-type GC risk. The most common GT haplotype (rs751402–rs2296147) showed protective effect for GC development (OR=0.73, 95%CI: 0.58–0.91, P=0.005), and especially for diffuse-type GC (OR=0.68, 95%CI: 0.52–0.90, P=0.006). Genetic effects on increased GC risk seemed to be enhanced by Helicobacter pylori infection, smoking and alcohol drinking, with corresponding adjusted ORs of 4.57, 2.42 and 2.50 for the rs751402 AG/AA variants, and of 5.32, 3.20 and 6.87 for the rs2296147 CC variant, but their interaction effects on GC risk didn''t reach statistically significance. ERCC5 rs751402 and rs2296147 polymorphisms might alter the risk of developing GC and especially the diffuse subtype. Further validation of our results in larger populations and additional studies evaluating their function impact are required. [Copyright &y& Elsevier]