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Iron metabolism plays an important role in maintaining cellular multiple biological functions. Dysfunction of iron homeostasis-maintaining systems was observed in many diseases, including cancer. Ribosomal L1 domain-containing 1 (RSL1D1) is an RNA-binding protein involved in multiple cellular processes, including cellular senescence, proliferation and apoptosis. However, the regulatory mechanism of RSL1D1 underlying cellular senescence and its biological process in colorectal cancer (CRC) is not clearly understood. Here, we report that RSL1D1 expression is downregulated by ubiquitin-mediated proteolysis in senescence-like CRC cells. RSL1D1, as an anti-senescence factor, is frequently upregulated in CRC, and elevated RSL1D1 prevents CRC cells from senescence-like phenotype, and correlated with poor prognosis of CRC patients. Knockdown of RSL1D1 inhibited cell proliferation, and induced cell cycle arrest and apoptosis. Notably, RSL1D1 plays important roles in regulating iron metabolism of cancer cells. In RSL1D1-knockdown cells, FTH1 expression was significantly decreased, while transferrin receptor 1 expression was increased, leading to intracellular ferrous iron accumulation, which subsequently promoted ferroptosis, indicated by the increased malondialdehyde and decreased GPX4 levels. Mechanically, RSL1D1 directly bounds with 3ʹ untranslated region of FTH1 and subsequently promoted the mRNA stability. Moreover, RSL1D1-mediated downregulation of FTH1 was also observed in H2O2-induced senescence-like cancer cells. Taken together, these findings support RSL1D1 plays an important role in regulating intracellular iron homeostasis in CRC, and suggest that RSL1D1 could be a potential therapeutic target for cancer treatment.

We examined the relationships among school climate, resilience, and depressive symptoms of 153 students at disciplinary alternative schools in China, focusing on the mediating effect of resilience and its two components of individual power and supportive power in the association between school climate and students' depressive symptoms. Participants completed the Perceived School Climate Inventory-Middle School, the Resilience Scale for Chinese Adolescents, and the Center for Epidemiologic Studies Depression Scale. Results indicated that the students' perception of school climate and their depressive symptoms were significantly and negatively correlated, and resilience and depressive symptoms were also significantly and negatively correlated. In addition, resilience significantly mediated the effect of school climate on the students' depressive symptoms. Finally, the effect of individual power in mediation of the relationship between school climate and depressive symptoms was greater than that of supportive power. The findings provide implications for school policy makers and mental health professionals by highlighting the need for promoting both a positive school climate and students' resilience and its component of individual power.

Bullying has become a social concern in schools in China, and school adjustment is an important factor affecting bullying. We explored the mediating role of social support in the relationship between school adjustment and bullying among 600 left-behind children in junior middle schools in Shandong Province, China. The students completed the School Adjustment Scale, the Multidimensional Scale of Perceived Social Support, and the Junior High School Bullying Questionnaire. Results showed significant differences in school adjustment, social support, and bullying between the children of families where only one parent had migrated to the city for work, and children of families where both parents had done so. School adjustment, social support, and bullying were significantly correlated among the left-behind children. Social support played a mediating role in the relationship between the school adjustment and bullying of these children. The results provide references for school teachers and family members to reduce bullying of left-behind children.

BACKGROUND: High glycemic index (GI) diets have been linked to elevated risk of cardiometabolic diseases. One possible underlying mechanism comes from high GI diet's potential to promote lipid peroxidation. OBJECTIVES: We aim to evaluate whether and to what extent dietary carbohydrate quality and quantity are associated with systemic levels of lipid peroxidation in females. METHODS: In this cross-sectional analysis of 2163 middle-aged women, a subset of the Shanghai Women's Health Study, we measured lipid peroxidation biomarkers F(2)-isoprostanes (F(2)-IsoPs) and its metabolite, 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (F(2)-IsoP-M), in urine. The quality of carbohydrate was defined by dietary GI, assessed using a validated FFQ via in-person interviews. A multivariable linear regression model with restricted cubic spline functions was used to evaluate the association of measured biomarkers with carbohydrate intake and dietary GI. RESULTS: After adjustment for potential confounding factors such as cigarette smoking, BMI, and comorbidities, among others, we found that F(2)-IsoP-M concentrations were positively associated with both carbohydrate intake and dietary GI. Carbohydrate intake and dietary GI were weakly correlated (r = 0.12). When further mutually adjusted for the 2 factors, the positive association with F(2)-IsoP-M remained statistically significant for GI (P = 0.004) but not for carbohydrate intake (P = 0.50). Compared with those in the 10th percentile of dietary GI, fold increases (95% CI) in F(2)-IsoP-M concentrations for those in the 30th, 50th, 70th, and 90th percentiles were 1.03 (1.00, 1.07), 1.06 (1.01, 1.10), 1.09 (1.03, 1.14), and 1.13 (1.05, 1.21), respectively. Moreover, there appeared a threshold regarding the association between dietary GI and F(2)-IsoP-M concentrations, with the dose-effect slope of GI being 2.3 times greater when GI was ≥75 relative to GI

Supplementary Figure 5: The specificity of RAV-18 to ADAM-9 protease activity

Supplementary Figure 4: In vivo treatment of RAV-18.

Advanced gastric cancer is one of the most aggressive gastrointestinal malignancies, and ADAM (A disintegrin and metalloproteinase)-9 is a cell-surface membrane glycoprotein with oncogenic properties that is overexpressed in several cancers. Herein, we investigated the biologic mechanism of ADAM9 in the progression, proliferation, and invasion of gastric cancer. First, we detected ADAM's expression, processing, and protease activity in gastric cancer cells. Protease activity was moderately correlated with ADAM9 protein expression, but was better related to a processed smaller molecular weight (84 kDa) form of ADAM9. Knockdown of ADAM9 or specifically targeted monoclonal antibody (RAV-18) suppressed cancer cell proliferation and invasion in high ADAM9-expressing cells, not in low ADAM9-expressing cells. RAV-18 showed in vivo antitumor activity in a gastric cancer xenograft model. Hypoxia (1% oxygen) induced ADAM9 expression and functional activity in low ADAM9-expressing gastric cancer cells that was inhibited by siRNA knockdown or RAV-18 antibody to levels in normoxic cells. Overall, our studies show that ADAM9 plays an important role in gastric cancer proliferation and invasion, and that while expressed in some gastric cancer cells at high levels that are responsive to functional inhibition and antitumor activity of a catalytic site–directed antibody, other gastric cancer cells have low levels of expression and only when exposed to hypoxia do ADAM9 levels increase and the cells become responsive to ADAM9 antibody inhibition. Therefore, our findings suggest that ADAM9 could be an effective therapeutic target for advanced gastric cancer. Mol Cancer Ther; 13(12); 3074–85. ©2014 AACR.

Supplementary Figure 1: Transcription level of ADAM9 in gastric cancer cell lines.

Supplementary Figure 2: Efficiency of siRNA transfection against ADAM-9, -10 and -17 in 3 gastric cancer cells.

Supplementary Figure 3: Adhesion assay after treatment of RAV-18.

Supplementary Figure Legends

Oral squamous cell carcinoma (OSCC) is mostly diagnosed at an advanced stage, with local and/or distal metastasis. Thus, locoregional and/or local control of the primary tumor is crucial for a better prognosis in patients with OSCC. Platelets have long been considered major players in cancer metastasis. Traditional antiplatelet agents, such as aspirin, are thought to be potential chemotherapeutics, but they need to be used with caution because of the increased bleeding risk. Podoplanin (PDPN)-expressing cancer cells can activate platelets and promote OSCC metastasis. However, the reciprocal effect of platelets on PDPN expression in OSCC has not been investigated. In this study, we found that direct contact with platelets upregulated PDPN and integrin β1 at the protein level and promoted invasiveness of human OSCC Ca9.22 cells that express low levels of PDPN. In another human OSCC HSC3 cell line that express PDPN at an abundant level, silencing of the

Although reproductive factors have been repeatedly associated with lung cancer risk, no study to date has directly evaluated the relationship with endogenous sex hormones nor with aromatase activity in postmenopausal never-smoking women. A case-control study of 397 incident lung cancer cases and their individually matched controls, nested within the Shanghai Women's Health Study, was conducted among postmenopausal women who were lifetime never smokers. Prediagnostic concentrations of sex hormones was quantitated using LC-MS/MS assays in plasma. The product-substrate molar ratio of estrone to androstenedione was used as an index of aromatase activity (IAA). Multivariable conditional logistic regression models were used to calculate odds ratios (ORs) for lung cancer. Baseline concentrations of estradiol, free testosterone and IAA were inversely associated with subsequent risk of lung cancer in multivariable-adjusted models. When further adjusted for body mass index, the inverse association with estradiol was attenuated and no longer statistically significant, but the association with free testosterone and IAA remained. In analyses confined to participants having never used menopausal hormone therapy in 376 case-control pairs, the inverse association with free testosterone and IAA was slightly strengthened. OR for the highest vs the lowest quartile of free testosterone was 0.55 (95% CI = 0.34-0.90; P

BACKGROUND Since several lines of evidence suggest that estrogens may be involved in lung carcinogenesis, it has been hypothesized that intake of phytoestrogens, similar in molecular structure to mammalian estrogens, may be associated with lung cancer development. OBJECTIVE To prospectively evaluate the association between phytoestrogen exposure and lung cancer risk in never-smoking females. DESIGN We conducted a nested case-control study within a population-based prospective cohort study of adult females. A total of 478 incident lung cancer cases and their individually matched controls were identified among never-smoking females after a mean follow-up of 15.6 years. Habitual intake of and internal exposure to phytoestrogens were assessed by repeated dietary surveys and urinary biomarkers, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer were estimated in conditional logistic regression models. RESULTS After adjustment for potential confounders, a moderate intake of dietary isoflavones was inversely associated with lung cancer risk in never-smoking females, with OR for the second quartile vs lowest quartile of intake being 0.52 (95% CI: 0.35, 0.76). Further increasing intake did not convey additional benefits, with ORs (95% CI) for the third and fourth quartiles being 0.53 (0.36, 0.78) and 0.47 (0.31, 0.72), respectively (P-overall < 0.001 and P-nonlinearity = 0.006). A similar association shape was seen when exposure to isoflavones was assessed by urinary biomarkers. ORs (95% CI) for the second, third and fourth quartiles vs lowest quartile of urinary isoflavone excretion were 0.57 (0.39, 0.83), 0.64 (0.44, 0.92) and 0.60 (0.41, 0.86), respectively. The inverse association plateaued beyond the second quartile, with P-overall = 0.04 and P-nonlinearity = 0.15. Urinary excretion of gut-microbiota-derived metabolites of lignans was not related to lung cancer risk. CONCLUSIONS The study suggests that moderately increasing intake of isoflavone-rich foods is associated with lower risk of lung cancer in never-smoking females.

Workers in semiconductor factories have occupational health risks from exposure to chemical substances. This work analyzed hazardous chemical substances in the key process of a semiconductor factory in China, and studied cancer and non-cancer health risks and occupational health risks of workers. Research results show that more than half of the processes contain compounds such as hydrogen fluoride, chlorine, hydrogen chloride, ammonia and 2-propanol, and their concentrations vary greatly depending on the process. The occupational exposure index (Ei) of some processes is greater than 1, which means that there are adverse occupational health risks, including wet etching (WETCH), physical vapour deposition (PVD), furnace process (FUR), chemicals storehouse (CS) and diffusion (from inspection area). The pollutants with a high contribution rate to Ei vary with the process, and WETCH (operating area) has the highest contribution rate of sulphuric acid (93.33%). The Hazard Quotient (HQi) of PVD and CS is far greater than 1, indicating that there is a non-cancer risk. The lifetime cancer risk (LCRi) of wastewater treatment and CS is greater than 10−4, which indicates a risk of cancer. The General Engineer has higher health risks than the Duty Engineer due to the higher exposure frequency.

The popularity of decoration and refurbishment of rental apartments in China may give rise to indoor VOC levels, posing health threats to tenants. A questionnaire was conducted on the renovation characteristics and tenant information of rental apartments in Beijing. The study selected 143 rental bedrooms to study the characteristics of HCHO and BTX (benzene, toluene and xylene) and assessed the health risks of tenants. The results showed that the median of HCHO concentration was 0.07 mg/m3, within one to three months of renovation. The concentration declined to 0.03 mg/m3 after one year. However, BTX concentration was increased by four times after one year of renovation, probably due to tenants’ move-in. The mean of inhalation lifetime cancer risk for HCHO and benzene was calculated as 1.15–3.63 (10−5) and 2.46–7.9 (10−5), respectively, indicating probable risk. The tenants’ health risks were: infant > teenager > adult and male > female. Benzene in rental homes posed the greater health risk to humans than previous studies conducted in ordinary residences. The results show that 45.29% of rental apartments are renovated before the new tenants move in, and 86.27% of tenants have a lease length of less than three years. These behaviours may cause exacerbation of pollutant levels in rental apartments.

OBJECTIVE: We aim to investigate whether and how lipid peroxidation markers are associated with height and obesity measures. METHODS: In two independent samples of women (Study-1, n=1005; Study-2, n=1158), systemic levels of lipid peroxidation were assessed by urinary markers F(2)-isoprostanes (F(2)-IsoPs) and its major metabolite (F(2)-IsoP-M), with GC/NICI MS assays. Anthropometric parameters were directly measured and were genetically estimated, used in the primary analysis and in a Mendelian randomization analysis in relation to lipid peroxidation, respectively, with general linear models. RESULTS: After adjusted for potential confounders, we found that measured adult height was inversely associated with levels of F(2)-IsoPs (β=−0.89, P

The underlying molecular mechanisms of cutaneous squamous cell carcinoma (cSCC) pathogenesis are largely unknown. In the present study, we aimed to evaluate the effect of coatomer protein complex subunit beta 2 (COPB2) expression on cSCC pathogenesis. Clinicopathological significance of COPB2 in cSCC was investigated by analyzing the Gene Expression Omnibus (GEO) database and through a retrospective cohort study of 95 cSCC patients. The effect of COPB2 expression on the biological behavior of cSCC cells was investigated both in vitro and in vivo. We found that COPB2 expression was significantly higher in cSCC samples than in normal skin samples. In our cohort, a considerable association was found between COPB2 expression and indicators of tumor immune microenvironment (TIME), such as histocompatibility complex class (MHC) I, and MHC II, CD4+/ CD8+ tumor-infiltrating lymphocytes. Additionally, COPB2 expression had an independent impact on worsened recurrence-free survival in our cohort. Furthermore, decreased proliferation, invasion, tumorigenic activities, and increased apoptosis were observed after COPB2 knockdown in cSCC cells. COPB2 may act as a potential oncogene and candidate modulator of the TIME in cSCC. Therefore, it can serve as a novel predictive prognostic biomarker and candidate immunotherapeutic target in cSCC patients.

Cancer therapy utilizing adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated remarkable clinical outcomes in hematologic malignancies. However, CAR T cell application to solid tumors has had limited success, partly due to the lack of tumor-specific antigens and an immune-suppressive tumor microenvironment. From the tumor tissues of gastric cancer patients, we found that intercellular adhesion molecule 1 (ICAM-1) expression is significantly associated with advanced stage and shorter survival. In this study, we report a proof-of-concept study using ICAM-1-targeting CAR T cells against gastric cancer. The efficacy of ICAM-1 CAR T cells showed a significant correlation with the level of ICAM-1 expression in target cells in vitro. In animal models of human gastric cancer, ICAM-1-targeting CAR T cells potently eliminated tumors that developed in the lungs, while their efficacy was more limited against the tumors in the peritoneum. To augment CAR T cell activity against intraperitoneal tumors, combinations with paclitaxel or CAR activation-dependent interleukin (IL)-12 release were explored and found to significantly increase anti-tumor activity and survival benefit. Collectively, ICAM-1-targeting CAR T cells alone or in combination with chemotherapy represent a promising strategy to treat patients with ICAM-1+ advanced gastric cancer., Graphical Abstract, In this study, we demonstrated the therapeutic potential of CAR T cells targeting ICAM-1 in preclinical models of systemic and intraperitoneal metastases of gastric cancer. A combination with paclitaxel or armoring CAR T cells with inducible IL-12 was found to significantly enhance the treatment effect of CAR T cells.

Objectives: Uremic pruritus is common in patients with chronic kidney disease (CKD). The retention of uremic solutes is thought to be associated with uremic pruritus. Meanwhile, activation of protease-activated receptor-2 (PAR-2) has been suggested to play an important role in pruritus. The present study was performed to investigate the effects of uremic solutes on the expression of PAR-2 in the skin. Methods: Indoxyl sulfate (IS), p-cresol (PC), and uremic sera from CKD patients were used to stimulate PAR-2 expression in normal human epidermal keratinocytes (NHEKs). Also, NHEKs were additionally pretreated with soybean trypsin inhibitor to evaluate its inhibitory effect on PAR-2 expression. Patterns of cutaneous PAR-2 expression were investigated in skin samples from five CKD patients and CKD mice. Results: In NHEKs, IS, PC, and sera from CKD patients significantly induced PAR-2 mRNA and protein expression. Soybean trypsin inhibitor significantly decreased PAR-2 mRNA and protein expression in NHEKs treated with IS, PC, and CKD sera. NHEKs treated with IS and PC exhibited significant increases in protease activity. Skin from both CKD patients and mice exhibited marked upregulation of PAR-2 expression compared to control skin. Conclusions: Results from the present study suggest that uremic solutes either directly or indirectly affect PAR-2 expression in the skin of CKD subjects, potentially playing an important role in the pathogenesis of uremic pruritus.

To explore the root factors in school bullying for fundamentally preventing school bullying, interpretative structural modeling is applied to construct the multilevel hierarchical structure model for influence factors in elementary and junior high school bullying. The results reveal that psychological factors and habits are the direct factors in elementary and junior high school bullying, law enforcement, physiological factors, and national legislation are the mediating factors, and the field and capital of family factors, school factors, and social factors are the root factors. According to the model analysis, it is suggested to construct the multiple collaboration mechanism for preventing school bullying from root factors.

Osteoporosis is a severe chronic skeletal disorder that affects older individuals, especially postmenopausal women. However, molecular biomarkers for predicting the risk of osteoporosis are not well characterized. The aim of this study was to identify combined biomarkers for predicting the risk of osteoporosis using machine learning methods. We merged three publicly available gene expression datasets (GSE56815, GSE13850, and GSE2208) to obtain expression data for 6354 unique genes in postmenopausal women (45 with high bone mineral density and 45 with low bone mineral density). All machine learning methods were implemented in R, with the GEOquery and limma packages, for dataset download and differentially expressed gene identification, and a nomogram for predicting the risk of osteoporosis was constructed. We detected 378 significant differentially expressed genes using the limma package, representing 15 major biological pathways. The performance of the predictive models based on combined biomarkers (two or three genes) was superior to that of models based on a single gene. The best predictive gene set among two-gene sets included

In-vitro and animal studies demonstrate that lipid peroxidation plays an important role in the pathogenesis of type 2 diabetes (T2D). However, human data from prospective studies are limited and contradictory. We used data originally collected in two nested case-control studies of cancer to prospectively evaluate whether systemic levels of lipid peroxidation were associated with incidence of T2D in 1917 women who were 40–70 years old and diabetes-free at baseline. Lipid peroxidation was measured by urinary F2-isoprostanes (F2-IsoPs) and its major metabolite 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M) with GC/NICI-MS assays. The Cox regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident T2D. After a median follow-up of 10.1 years, 187 women were diagnosed with T2D. Urinary concentrations of both F2-IsoPs and F2-IsoP-M were significantly higher in T2D cases than in non-cases. Both biomarkers were positively associated with subsequent risk of T2D in multivariable-adjusted Cox models. When further adjusted for body mass index (BMI), the positive association with F2-IsoP-M was attenuated and no longer statistically significant, whereas the association with F2-IsoPs remained (P for overall significance < 0.001). HR for T2D was 1.68 (95% CI: 1.13, 2.51) for the highest vs the lowest quartile of F2-IsoPs. Moreover, this association appeared more pronounced among women with higher BMI. In summary, our study suggests that F2-IsoPs could be of significance in T2D risk prediction among middle-aged and elderly women.

BACKGROUND Sparc/osteonectin, cwcv and kazal-like domain proteoglycan 1 (SPOCK1) has been reported to function as an oncogene in a variety of cancer types. Increasing evidence suggests that SPOCK1 contributes to the metastatic cascade, including invasion, epithelial-mesenchymal transition (EMT) and micro-metastasis formation. As yet, however, the underlying mechanism is not clearly understood. Here, we evaluated the expression and clinicopathological significance of SPOCK1 in primary pancreatic cancer (PC) specimens and explored the mechanisms underlying SPOCK1-mediated PC cell growth and metastasis. METHODS The clinical relevance of SPOCK1 was evaluated in 81 patients with PC. The effect of SPOCK1 on proliferation, cell cycle progression, EMT and metastasis was examined in vitro and in vivo. The molecular mechanisms involved in SPOCK1-mediated regulation of NF-κB-dependent EMT were assessed in PC cell lines. RESULTS We found that SPOCK1 expression was increased in PC tissues and was associated with lymph node metastasis. Silencing or exogenous overexpression of SPOCK1 markedly altered the proliferation of PC cells through cell cycle transition. Overexpression of SPOCK1 promoted PC cell migration and invasion by regulating EMT progression. Moreover, we found that SPOCK1 contributes to EMT and metastasis by activating the NF-κB signalling pathway via direct interaction with IκBα. After NF-κB pathway inhibition by BAY11-7082, we found that PC cell motility and EMT induced by SPOCK1 were reversed. CONCLUSION From our data we conclude that SPOCK1 promotes PC metastasis via NF-κB-dependent EMT by interacting with IκBα. This newly identified mechanism may provide novel clues for the (targeted) treatment of PC patients.

Oral squamous cell carcinoma (OSCC) frequently invades the maxillary or mandibular bone, and this bone invasion is closely associated with poor prognosis and survival. Here, we show that CCL28 functions as a negative regulator of OSCC bone invasion. CCL28 inhibited invasion and epithelial-mesenchymal transition (EMT), and its inhibition of EMT was characterized by induced E-cadherin expression and reduced nuclear localization of β-catenin in OSCC cells with detectable RUNX3 expression levels. CCL28 signaling via CCR10 increased retinoic acid receptor-β (RARβ) expression by reducing the interaction between RARα and HDAC1. In addition, CCL28 reduced RANKL production in OSCC and osteoblastic cells and blocked RANKL-induced osteoclastogenesis in osteoclast precursors. Intraperitoneally administered CCL28 inhibited tumor growth and osteolysis in mouse calvaria and tibia inoculated with OSCC cells. RARβ expression was also increased in tumor tissues. In patients with OSCC, low CCL28, CCR10, and RARβ expression levels were highly correlated with bone invasion. Patients with OSCC who had higher expression of CCL28, CCR10, or RARβ had significantly better overall survival. These findings suggest that CCL28, CCR10, and RARβ are useful markers for the prediction and treatment of OSCC bone invasion. Furthermore, CCL28 upregulation in OSCC cells or CCL28 treatment can be a therapeutic strategy for OSCC bone invasion.

Low temperature coal tar contained a large amount of phenols, aromatic hydrocarbons and alkanes; the separation of phenols from coal tar has a great significance to the deep processing of coal tar. In this work, the separation of m-cresol from cumene and n-heptane by liquid–liquid extraction using ionic liquids (ILs) as extractants was studied. The suitable ILs were screened by conductor-like screening model for real solvents (COSMO-RS) model and the liquid–liquid phase equilibrium (LLE) experiments were to verify the accuracy of the screening results. The extraction conditions such as extraction time, extraction temperature and mass ratio of ILs to model oils were evaluated. An internal mechanism of the m-cresol extract by ILs was revealed by COSMO-RS calculation and FT-IR. The results showed that the selected ILs can extract m-cresol effectively from cumene and n-heptane, 1-ethyl-3-methylimidazolium acetate (emimCH3COO) was the best extraction solvent. A hydrogen bond between anion of ILs and phenolic hydroxyl groups was observed. M-cresol in model oils could be extracted with extraction efficiencies up to 98.85% at an emimCH3COO: model oils mass ratio of 0.5 and 298.15 K, emimCH3COO could be regenerated and reused for 4 cycles without obvious decreases in extraction efficiency and extractant mass.

Background Gastric cancer (GC) is a major leading cause of cancer mortality worldwide. Polyadenylate (poly(A))-binding protein (PABP)-interacting protein 1 (Paip1) is a key regulator in the initiation of translation; however, its role in GC remains to be investigated. Purpose The purpose of this study is to determine Paip1 expression levels and investigate its underlying molecular mechanism in GC. Patients and methods In the present study, a total of 90 GC samples and 90 adjacent noncancerous tissues were used to examine the expression of Paip1. In order to gain a deep insight into the molecular mechanism of Paip1 in GC, the Paip1 siRNA sequences were transfected into GC cell lines (MGC-803 and SGC-7901), respectively. Meanwhile, Paip1 plasmid was used to mediate overexpression of Paip1. Cell proliferation were examined via colony formation assay, EdU assay and flow cytometry assay. Cell metastasis were discovered via wound healing assay and Transwell assays. In addition, key EMT makers were detected by Western blotting assay. Results In this study, Paip1 expression was observed to be upregulated in GC and was associated with shorter overall survival. Knockdown of Paip1 inhibited cell proliferation, migration and caused cell cycle arrest in GC cells, whereas its overexpression reversed these effects. Another mechanistic study showed that Paip1 overexpression promoted EMT progression and regulated its targets expression. Conclusion High expression of Paip1 plays a significant role in the progression of GC and may be a potential biomarker of poor prognosis as well as a therapeutic target.

This study focused on mortalin expression and its relevance to the prognosis in serous ovarian carcinoma, mortalin modulated cell malignant proliferation and EMT progression via Wnt/β-Catenin signaling pathway. In this study, data obtained from Oncomine database, Cancer Cell Line Encyclopedia (CCLE) analysis and Immunohistochemical (IHC) staining was used to assess the expression of mortalin in serous ovarian carcinoma. The prognostic value of mortalin was analyzed using Meier plotter database and Kaplan-Meier. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay, immunofluorescence (IF) staining, and colony formation assay were used to detect cell reproductive capacity. SK-OV-3 cell motility and epithelial-mesenchymal transition (EMT) were measured by wound-healing, migration and western-blot assays. Data from Oncomine showed that mortalin was highly expressed in serous ovarian carcinomas compared with corresponding normal controls. Similar results were found in CCLE analysis and in clinical specimens. High mortalin expression was associated with high histological grade and worse overall survival (OS) rate. The results of MTT analyses, IF staining, and colony formation assay indicated that MKT-077 (1-Ethyl-2-[[3-ethyl-5-(3-methyl-2(3H)-benzothiazolylidene)-4-oxo-2-thiazolidinylidene] methyl]-pyridinium chloride) suppressed the viability of SK-OV-3 cells. Besides, mortalin suppression restrained cell EMT progression by Wnt/β-Catenin signaling pathway. Taken together, mortalin is over-expressed in serous ovarian carcinoma. High mortalin expression could be a candidate for the prognostic indicator and a biomarker in serous ovarian carcinoma.