Osteocalcin inhibits myocyte aging through promotion of starvation-induced autophagy via IL-6/STAT3 signaling.

This study aimed to investigate the effects and mechanisms of osteocalcin on autophagy in myoblasts, as well as its possible therapeutic effects in aging muscle. Starved murine myoblast C2C12 cells with or without interleukin (IL)-6 siRNA were treated with osteocalcin. Expression of the autophagy protein marker LC3, as well as IL-6 and phosphorylated STAT3 were detected by immunoblotting, immunofluorescence, or immunohistochemistry. Autophagosomes were observed with transmission electron microscopy. Levels of reactive oxygen species (ROS) were detected by flow cytometry. Fasted young mice were injected intraperitoneally with osteocalcin, with or without the JAK inhibitor CP-690550 to inhibit IL-6 signaling. Older mice were treated with osteocalcin and muscle mass, grip strength and muscle structure were assessed. The results revealed that compared to control and serum-starved cells, osteocalcin treatment significantly increased the relative expression of LC3-II/LC3-I protein, the numbers of autophagosomes, and levels of intracellular ROS. Osteocalcin injection in mice also resulted in increased relative LC3-II/LC3-I protein expression and autophagosome numbers. Osteocalcin treatment significantly increased the secretion of IL-6 in muscle cells and tissue, and activated STAT3 signaling. Moreover, knockdown of IL-6 or blocking IL-6 signaling inhibited the phosphorylation of STAT3, and further inhibited autophagy in starved myoblasts and fasting-treated murine muscle tissue. In addition, osteocalcin treatment significantly increased muscle mass and grip strength in both aged mice and aged fasting mice. In conclusion, the inhibition of osteocalcin on muscle cell aging is accompanied by the induction of IL-6-STAT3-dependent autophagy, indicating osteocalcin might be a promising therapeutic candidate for aging-related myopathies.

Depressive Symptoms and Cognitive Decline Among Chinese Rural Elderly Individuals: A Longitudinal Study With 2-Year Follow-Up.

Background: Depressive symptoms and mild cognitive impairment (MCI) are highly prevalent in rural China. The study aimed to investigate the longitudinal associations between changes in depressive symptoms and cognitive decline and MCI incidence among Chinese rural elderly individuals. Methods: A 2-year follow-up study was conducted among 1,477 participants from the Anhui Healthy Longevity Survey (AHLS). Depressive symptoms were assessed by the 9-item Patient Health Questionnaire (PHQ-9), and cognitive status was evaluated by the Mini Mental State Examination (MMSE). Multivariable linear regression and logistic regression were employed. Results: Every 1-unit PHQ-9 score increase was significantly associated with more cognitive decline (ß = 0.157, 95% CI: 0.092, 0.221, p < 0.001) and a higher risk of MCI incidence (OR = 1.063, 95% CI: 1.025, 1.103, p = 0.001). The participants who experienced worsening of depression symptoms had a larger decline in the 2-year MMSE score (ß = 0.650, 95% CI: 0.039, 1.261, p = 0.037) and elevated risks of incident MCI (OR = 1.573, 95% CI: 1.113, 2.223, p = 0.010). Limitations: Screening tools rather than standard diagnostic procedures were used in the study. Moreover, the long-term associations still need further exploration since the follow-up time was short. Conclusions: Increased depressive symptoms were associated with more cognitive decline and higher risks of incident MCI among Chinese rural residents.

Chest CT features associated with the clinical characteristics of patients with COVID-19 pneumonia.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) has rapidly swept across the world. This study aimed to explore the relationship between the chest CT findings and clinical characteristics of COVID-19 patients. METHODS: Patients with COVID-19 confirmed by next-generation sequencing or RT-PCR who had undergone more than 4 serial chest CT procedures were retrospectively enrolled. RESULTS: This study included 361 patients - 192 men and 169 women. On initial chest CT, more lesions were identified as multiple bilateral lungs lesions and localised in the peripheral lung. The predominant patterns of abnormality were ground-glass opacities (GGO) (28.5%), consolidation (13.0%), nodule (23.0%), fibrous stripes (5.3%) and mixed (30.2%). Severe cases were more common in patients with a mixed pattern (21.1%) and less common in patients with nodules (2.4%). During follow-up CT, the mediumtotal severity score (TSS) in patients with nodules and fibrous strips was significantly lower than that in patients with mixed patterns in all three stages (p < .01). CONCLUSION: Chest CT plays an important role in diagnosing COVID-19. The CT features may vary by age. Different CT features are not only associated with clinical manifestation but also patient prognosis. Key messages The initial chest CT findings of COVID-19 could help us monitor and predict the outcome. Nodules were more common in non severe cases and had a favorable prognosis. The mixed pattern was more common in severe cases and usually had a relatively poor outcome.

Upregulated ß-arrestin1 predicts poor prognosis and promotes metastasis via AKT/ERK signaling pathway in gastric cancer.

BACKGROUND: ß-Arrestins have been found to regulate cell proliferation, invasion and migration; transmit anti-apoptotic survival signals; and affect other characteristics of tumours. However, their role in gastric cancer (GC) is not clear. We investigated the role and mechanism of ß-arrestins in the regulation of GC. METHODS: We first examined ß-arrestins mRNA levels in 17 pairs of GC tissues by qRT-PCR. We also used immunohistochemistry to further examine the expression of ß-arrestins in 60 paraffin-embedded primary GC tissues and 20 normal gastric tissues. Then, the function of ß-arrestin1 was investigated in vitro and in vivo. RESULTS: ß-Arrestin1 was upregulated in GC tissue and was associated with tumour stage, lymph node metastasis, invasion depth and patient sex. High expression of ß-arrestin1 expression predicted poor prognosis in GC. ß-Arrestin1 promoted GC cell proliferation, migration and invasion, and it suppressed E-cadherin expression and upregulated Vimentin expression via AKT/ERK signalling pathway. The in vivo metastasis assays showed that knockdown of ß-arrestin1 reduced lung metastasis and inhibited EMT. CONCLUSION: The upregulation of ß-arrestin1 predicts poor prognosis and promotes metastasis and epithelial-mesenchymal transition in GC through AKT/ERK signalling pathway. This study may provide therapeutic advances for the treatment and early diagnosis of patients with metastatic GC.

The Wnt3a/ß-catenin/TCF7L2 signaling axis reduces the sensitivity of HER2-positive epithelial ovarian cancer to trastuzumab.

Epithelial ovarian cancer (EOC) is one of the most common and lethal gynecological cancers. Novel therapeutic agents have been developed for EOC, but patient survival remains poor. Trastuzumab has been approved for breast and gastric cancers with high expression of human epidermal growth factor receptor 2 (HER2), but it has not achieved any clinical success in EOC. Dysregulated Wnt/ß-catenin signaling is involved in cancer development, but whether it plays a role in EOC resistance to trastuzumab remains largely unknown. Here, we observed that high expression of Wnt3a, ß-catenin and TCF7L2, which can form a signaling axis in the Wnt/ß-catenin pathway, commonly existed in HER2-positive EOC tissue samples and was correlated with a poor patient prognosis. Cell proliferation and migration assays and nude mouse xenograft model experiments demonstrated that the Wnt3a/ß-catenin/TCF7L2 signaling axis promoted tumor cell growth and metastasis and reduced tumor sensitivity to trastuzumab. Analysis of downstream Akt signaling suggested that the function of the Wnt3a/ß-catenin/TCF7L2 signaling axis was mediated, at least in part, through increasing Akt phosphorylation. Overall, this study reveals a crucial role for the Wnt3a/ß-catenin/TCF7L2 signaling axis in EOC resistance to trastuzumab and the potential application of HER2-targeted drugs combined with inhibitors of this signaling axis for EOC treatment.

Intrinsically altered lung-resident γδT cells control lung melanoma by producing interleukin-17A in the elderly.

Cancer is an age-associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung-resident γδT cells was significantly increased with altered gene expression in aged mice (20-24 months) versus young mice (10-16 weeks). Aged lung Vγ4+ and Vγ6+ γδT cells predominantly produced interleukin-17A (IL-17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4+ and Vγ6+ γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103. The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL-17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL-17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the anti-tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co-housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age-dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti-tumor immunotherapy.

The association between weight fluctuation and all-cause mortality: A systematic review and meta-analysis.

BACKGROUND: Many observational studies have reported an association between weight fluctuation and all-cause mortality. However, the conclusions obtained from these studies have been unclear. OBJECTIVE: The current meta-analysis aimed to clarify the association between weight fluctuation and all-cause mortality. DATA SOURCE: We electronically searched PubMed, Embase, and Web of Science for articles reporting an association between weight fluctuation and all-cause mortality that were published before April 30, 2018. STUDY APPRAISAL AND SYNTHESIS METHODS: The methodological quality of each study was appraised using the modified Newcastle Ottawa Quality Assessment Scale. The hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were extracted from the included studies and pooled using random-effect models. Meta-regression approaches were also performed to explore sources of between-study heterogeneity. RESULTS: A total of 15 studies were eligible for the current meta-analysis. The pooled overall HR for all-cause mortality in the group with the greatest weight fluctuations compared with the most stable weight category was 1.45 (95% CI: 1.29-1.63). Considerable between-study heterogeneity was observed, some of which was partially explained by the different follow-up durations used by the included studies. Moreover, publication bias that inflated the risk of all-cause mortality was detected using Egger's test (P = .001). CONCLUSION: Weight fluctuation might be associated with an increased risk of all-cause mortality.

MiR-92a antagonized the facilitation effect of extracellular matrix protein 1 in GC metastasis through targeting its 3'UTR region.

MicroRNAs were known to play very important roles in human diseases, and have attracted great interests of research scientists in medicine, toxicology and functional foods. Gastric carcinoma (GC) remains one of the most common and lethal types of malignancy worldwide. However, the molecular mechanism of GC and the role of microRNAs in GC development remain unclear. The expression of extracellular matrix protein 1 (ECM1) is up-regulated in many cancer types, but its functional role is inconstant. In the present study, we aimed to investigate the correlation between GC development and ECM1 expression, along with its regulation by microRNAs. Immunohistochemical results showed that ECM1 was up-regulated in GC tissues and ECM1 expression level was negatively correlated with the prognosis of GC. ECM1 was found to promote gastric cancer cell metastasis in cell migration assays by facilitating the expression of proteins involved in epithelial-mesenchymal transition (EMT). MiR-92a was recognized for the first time to suppress the migration of human GC cells by directly targeting to the 3'UTR of ECM1 gene in a dual-luciferase reporter assay. These results highlighted the antagonistic roles of ECM1 and miR-92a in GC development, which may serve as a new target for gastric cancer.

Dendritic cell-targeted CD40 DNA vaccine suppresses Th17 and ameliorates progression of experimental autoimmune glomerulonephritis.

The CD40-CD40L costimulatory pathway is critical for T cell activation in autoimmune disease. We have previously found that blocking the CD40-CD40L pathway using a dendritic cell-targeted CD40 DNA (DEC-CD40) vaccine prevented the development of Heymann nephritis. In this study, we explored the effect of a DEC-CD40 vaccine in the treatment of experimental autoimmune glomerulonephritis (EAG), an animal model of human Goodpasture's disease induced by antigen α3IV-NC1. DEC-CD40 vaccine given at week 3 and week 6 after 3IV-NC1 injection reduced kidney structural and functional injury significantly in EAG. DEC-CD40 vaccination suppressed Th17 cell numbers and Th17 immune responses in kidney and spleen, but did not alter Th1 cells number and responses. Serum derived from rats with DEC-CD40 vaccination suppressed Th17 differentiation, but not Th1 differentiation in vitro. Furthermore, B cell activation, driven by Th17 cytokines, was suppressed by serum from rats vaccinated with DEC-CD40. A DNA vaccine encoding CD40 and targeting dendritic cell, ameliorates kidney injury in both early and late stages in EAG rats, indicating DEC-CD40 vaccination has a therapeutic role in EAG. Its effect is associated with the reduction of Th17 differentiation and Th17-mediated B cell activation.

Paraoxonase 3 is involved in the multi-drug resistance of esophageal cancer.

BACKGROUND: Drug resistance prevents the effective treatment of cancers. DNA methylation has been found to participate in the development of cancer drug resistance. METHODS: We performed the wound-healing and invasion assays to test the effect of the paraoxonase gene PON3 on esophageal cancer (EC) cells. In addition, in vivo EC-derived tumor xenografts in nude mice were generated to test the effect of PON3 on the chemoresistance of EC cells. RESULTS: We found that PON3 is hypermethylated in drug-resistant EC cell line K150, which in-return down-regulates its expression. The following experiments by the forced changes of PON3 level in vitro and in vivo demonstrated that the PON3 expression negatively correlates with drug resistance in EC cells. Further wound-healing and invasion assays showed that PON3 suppresses the migration and invasion of EC cells. CONCLUSION: Our data established that PON3 is associated with the EC drug resistance, which may serve as a biomarker for the potential therapeutic treatment of EC.

Glycemic reduction alters white blood cell counts and inflammatory gene expression in diabetes.

OBJECTIVE: Systemic inflammation contributes to cardiovascular disease in patients with type 2 diabetes, and elevated white blood cell (WBC) counts are an established risk factor. Our goal is to describe changes in WBCs and inflammatory markers after glycemic reductions in diabetes. RESEARCH DESIGN AND METHODS: This study enrolled 63 subjects with poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) ≥8% [64 mmol/mol]. Circulating granulocytes and mononuclear cells were separated by histopaque double-density protocol. Inflammatory markers from these isolated WBCs were assessed at baseline and after 3 months of medical management. RESULTS: After 3 months, significant glycemic reduction, defined as a decrease in HbA1c ≥ 1.5%, occurred in 42 subjects. Fasting plasma glucose decreased by 47% (165.6 mg/dL), and HbA1c decreased from 10.2 ±â€¯1.8 to 6.8 ±â€¯0.9. Glycemic reductions were associated with a 9.4% decrease in total WBC counts, 10.96% decrease in neutrophils, and 21.74% decrease in monocytes. The mRNA levels of inflammatory markers from granulocytes and mononuclear cells decreased, including receptor for advanced glycation endproducts; S100 calcium binding proteins A8, A9, A12; krüppel-like factor 5; and IL-1. Also, circulating levels of IL-1ß and C-reactive protein decreased. Insulin dose was a mediator between HbA1c and both total WBC and neutrophil counts, but not changes in WBC inflammatory markers. In contrast, the 17 subjects without significant glycemic reductions showed no significant differences in their WBC counts and proteins of inflammatory genes. CONCLUSION: Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

Clinicopathological and prognostic significance of circulating tumor cells in patients with lung cancer: a meta-analysis.

BACKGROUND: The prognostic significance of circulating tumor cells in patients with lung cancer is controversial. Therefore, we aimed to comprehensively and quantitatively assess the prognostic role of CTCs in patients with lung cancer. METHODS: The relevant literature was searched using PubMed, the Cochrane database and the China National Knowledge Internet database (up to June 2016). Using Review Manager 5.1.2, a meta-analysis was performed using hazard ratio (HR), odds ratio (OR) and 95% confidence interval (CI) as effect values. RESULTS: Thirty studies comprising 2,060 patients with lung cancer were analyzed. The pooled HR values showed that circulating tumor cells were significantly correlated with overall survival (HR =2.63, 95% CI [2.04, 3.39]) and progression-free survival (HR =3.74, 95% CI [2.49, 5.61]) in these patients. Further subgroup analyses were conducted and categorized by sampling time, detection method, and histological type; these analyses showed the same trend. The pooled OR values showed that circulating tumor cells were associated with non small cell lung cancer stage(OR = 2.11, 95% CI [1.42, 3.14]), small cell lung cancer stage (OR = 10.91, 95% CI [4.10, 29.06]), distant metastasis (OR =7.06, 95%CI [2.82, 17.66]), lymph node metastasis (OR =2.31, 95% CI [1.19,4.46]), and performance status(OR =0.42, 95%CI [0.22, 0.78]). CONCLUSION: The detection of circulating tumor cells in the peripheral blood of patients with lung cancer can be indicative of a poor prognosis.

Analysis of serum undercarboxylated osteocalcin level in rats with type 2 diabetes mellitus and the correlation with cognitive impairment.

The aim of the study was to investigate the correlation between the serum undercarboxylated osteocalcin (ucOC) level and the blood biochemistry and cognitive impairment in rats with type 2 diabetes mellitus (T2DM). Sprague-Dawley (SD) rats were randomly divided into the normal control group (NC) and type 2 DM group. DM group received the high-fat and high-sugar diet combined with the intraperitoneal injection of low-dose STZ to establish the type 2 DM rat model. After 12 weeks of feeding, a Morris water maze was used to observe the rats' cognitive ability, and the levels of blood lipid, ucOC, insulin and adiponectin in the two groups were measured. The results showed that blood glucose of rats in DM group was increased significantly at 2-12 weeks (p<0.01) and the body weight was significantly increased at 4-12 weeks (p<0.01). The levels of serum triglyceride (TG), total cholesterol, low-density lipoprotein and insulin in rats in DM group were significantly increased compared with those in NC group (p<0.01) and the levels of high-density lipoprotein, adiponectin and ucOC were significantly decreased compared with those in the NC group (p<0.01). The place navigation and spatial exploration capacities of rats in DM group were significantly decreased compared with those in NC group (p<0.01). In the DM group, the place navigation and spatial exploration capacities of rats in the low ucOC group were significantly decreased compared with those in the high ucOC group (p<0.01). Additionally, single-factor correlation analysis revealed that ucOC was negatively correlated with blood glucose, TG and escape latency (p<0.01), but was positively correlated with adiponectin, residence time in target quadrant and traversing times (p<0.05 or p<0.01). In conclusion, the decreased serum ucOC level in rats with type 2 diabetes mellitus has a certain correlation with cognitive impairment.

A Risk Factor Analysis of Cognitive Impairment in Elderly Patients with Chronic Diseases in a Chinese Population.

BACKGROUND This study analyzed the risk factors of cognitive impairment (CI) in elderly patients with chronic diseases. MATERIAL AND METHODS In total of 385 elderly patients with chronic diseases were selected and assigned into CI and normal groups. The activities of daily living (ADL), global deterioration scale (GDS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), patient-generated subjective global assessment (PG-SGA), and mini nutritional assessment (MNA) were performed to analyze the differences between the 2 groups. Logistic regression analysis was conducted for risk factors of CI in elderly patients with chronic diseases. RESULTS There were differences in age, education level, type 2 diabetes mellitus, multifocal cerebral infarction, hearing, and eyesight between CI and normal groups. Patients in the CI group showed more CD4+ cells, more admission times, and higher GDS scores than the normal group. Also, MMSE and MoCA scores revealed differences in total score, directive force, attention and calculating ability, language, delayed memory, reading comprehension, writing, and visual-spatial ability between the 2 groups. The number of B and CD8+ cells, ADL, and MNA scores were protective factors, while cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age were risk factors of CI in elderly patients with chronic diseases. CONCLUSIONS Our study provides evidence that cerebral infarction history, number of CD4+ cells, admission times, GDS score, and age are risk factors of CI in elderly patients with chronic diseases.

Commensal microbiota maintains alveolar macrophages with a low level of CCL24 production to generate anti-metastatic tumor activity.

Microbiota maintains host tissue homeostasis and influences tissue-resident macrophages. However, the mechanisms by which commensal bacteria in regulating the alveolar macrophages remain unclear. Here, by using an antibiotic-treated (Abt) mouse model, we found commensal bacteria depletion induced lower frequencies and numbers of alveolar macrophages. This effect was accompanied by the altered levels of genes involved in several biological pathways, including M2 macrophage polarization, as determined by gene expression analysis. Alveolar macrophages from the Abt mice had higher protein and gene levels of Arg1, CCL24, IL-13, IL-10, IL-6 and IL-1ß, which could be recovered to normal levels by reconstructing commensal bacteria in the upper respiratory of Abt mice. Moreover, alveolar macrophages performed significant enhancement of M2 functions, especially CCL24 secretion, in the Abt mice challenged with B16/F10 melanoma. Adoptive transfer of normal alveolar macrophages or antibody neutralization of CCL24 significantly recovered the decrease of γδT17 cells and rescued the defect anti-tumor response of Abt mice, indicating the elevated amount of alveolar macrophage-derived CCL24 inhibited γδT cell mediated anti-tumor response. In conclusion, we demonstrated the ability of commensal bacteria to maintain alveolar macrophages with a low level of CCL24 production, which was necessary for the normal anti-tumor response in the lung.

Lung-resident γδ T cells and their roles in lung diseases.

γδ T cells are greatly enriched in mucosal and epithelial sites, such as the skin, respiratory, digestive and reproductive tracts, and they are defined as tissue-resident immune cells. In these tissues, the characteristics and biological roles of γδ T cells are distinguished from each other. The lungs represent the most challenging immunological dilemma for the host, and they have their own effective immune system. The abundance of γδ T cells, an estimated 8-20% of resident pulmonary lymphocytes in the lung, maintains lung tissue homeostasis. In this review, we summarize the recent research progress regarding lung-resident γδ T cells, including their development, residency and immune characteristics, and discuss the involvement of γδ T cells in infectious diseases of the lung, including bacterial, viral and fungal infections; lung allergic disease; lung inflammation and fibrosis; and lung cancer.

Relationship between epithelial cell adhesion molecule (EpCAM) overexpression and gastric cancer patients: A systematic review and meta-analysis.

OBJECTIVES: The epithelial cell adhesion molecule (EpCAM) is one of the most commonly used markers of cancer stem cells (CSCs), but the clinical and prognostic significance of EpCAM in gastric cancer (GC) remains disputable. Motivated by heterogeneous and inconclusive results, we conducted a systematic review and meta-analysis to systematically summarize and elucidate the association between EpCAM overexpression and GC patients. METHODS: The PubMed, Cochrane Library, Medline, Web of Knowledge and the China National Knowledge Infrastructure (CNKI) databases were searched to identify relevant studies. The RevMan 5.3 software was used for the meta-analysis. Fixed-effects or random-effects models were applied depending on the presence of heterogeneity. The pooled odds ratio (ORs) and 95% confidence intervals (CIs) were applied to estimate the associations between EpCAM and gastric cancer. For the significant heterogeneity studies, sensitivity analyses were applied based on the population to test the robustness of the pooled results and identify possible sources of heterogeneity. RESULTS: A total of 11 studies including 1960 GC patients met our inclusion criteria. The results of the meta-analyses revealed that there were significant differences in EpCAM overexpression and tumour size (OR = 2.97, 95% CI: 2.13~4.13, P < 0.00001), the nature of the tissue (OR = 80.30, 95% CI: 29.21~220.81, P < 0.00001), lymph node metastasis (OR = 2.78, 95% CI: 1.23~6.27, P = 0.01), and the cumulative 5-year overall survival rate (OR = 0.54, 95% CI:0.29~0.99, P = 0.05). No significant associations were identified between EpCAM overexpression and gender (OR = 0.89, 95% CI: 0.66~1.19, P = 0.43), age (OR = 1.13, 95% CI: 0.58~2.20, P = 0.73), tumour stage (OR = 2.26, 95% CI: 0.79~6.45, P = 0.13), distant metastasis (OR = 2.15, 95% CI: 0.20~22.69, P = 0.52), TNM stage (OR = 5.14, 95% CI: 0.77~34.37, P = 0.09), Lauren type (OR = 1.18, 95% CI: 0.08~16.45, P = 0.9), differentiation (OR = 1.88, 95% CI: 0.65~5.41, P = 0.24). However, due to significant heterogeneity in tumor stage, lymph node metastasis, TNM stage, differentiation and Lauren type, these results should be taken carefully. CONCLUSIONS: The meta-analysis demonstrated that the expression of EpCAM in the gastric cancer group was greater than that in the control group. Moreover, EpCAM overexpression was associated with larger tumour size, lymphnode metastasis and worse prognosis in gastric cancer. Due to significant heterogeneity, the sensitivity analysis suggests that population factor may be an important source of heterogeneity, and these results should be treated with caution. EpCAM may be useful as a novel prognostic factor, and large-scale and well-designed studies are needed to validate our results in the future.

MiR-20a-5p promotes radio-resistance by targeting Rab27B in nasopharyngeal cancer cells.

BACKGROUND: MicroRNAs (miRNAs) was reported to be involved in cancer radio-resistance, which remains a major obstacle for effective cancer therapy. METHODS: The differently expressed miRNAs were detected by RNA-seq experiment in nasopharyngeal cancer (NPC) cells. MiR-20a-5p was selected as our target, which was subject to finding its target gene Rab27B via bioinformatics analysis. The qRT-PCR, western blot and the luciferase reporter assays were performed to confirm Rab27B as the target of miR-20a-5p. In addition, the roles of miR-20a-5p in NPC radio-resistance were detected by transfection of either miR-20a-5p-mimic or miR-20a-5p-antagomiR. The involvement of Rab27B with NPC radio-resistance was also detected by the experiments with siRNA-mediated repression of Rab27B or over-expression of GFP-Rab27B. Wound healing and invasion assays were performed to detect the roles of both miR-20a-5p and Rab27B. RESULTS: MiR-20a-5p promotes NPC radio-resistance. We identified that its target gene Rab27B negatively correlates with miR-20a-5p-mediated NPC radio-resistance by systematic studies of a radio-sensitive (CNE-2) and resistant (CNE-1) NPC cell lines. Repression of Rab27B by siRNA suppresses cell apoptosis and passivates CNE-2 cells, whereas over-expression of Rab27B triggered cell apoptosis and sensitizes CNE-1 cells. CONCLUSIONS: MiR-20a-5p and its target gene Rab27B might be involved in the NPC radio-resistance. Thus the key players and regulators involved in this pathway might be the potential targets for developing effective therapeutic strategies against NPC.