MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the invasion and migration of breast cancer.

Interleukin-8 (IL-8), which is secreted by cancer cells undergoing epithelial-mesenchymal transition (EMT), can promote EMT in adjacent epithelial-like cells. MicroRNAs (miRNAs/miRs) can affect the expression of target genes via binding to their 3'-untranslated regions (3'-UTRs), which may subsequently affect the biological behaviors of cancer cells. In our previous study, miR-520c-3p was predicted to directly target the 3'-UTR of IL-8. Therefore, the present study was carried out to investigate whether miR-520c-3p can interact with the IL-8 gene and regulate the EMT of breast cancer cells. Web-based prediction algorithms were used to identify miRNAs that potentially target the IL-8 transcript. Luciferase reporter assays were used to confirm the targeting of IL-8 by miR-520c-3p. Reverse transcription-quantitative PCR and western blot analyses were used to examine the levels of IL-8 and EMT-related genes in breast cancer cells. The functional impact of miR-520c-3p on EMT phenotype was evaluated using Transwell and wound-healing assays, and rescue experiments were conducted by overexpressing IL-8 to determine its effect on cell properties. miR-520c-3p was predicted by all three databases, which strongly suggested its interaction with the 3'-UTR of IL-8. The relative Renilla luciferase activity of luciferase reporter construct containing the wild-type 3'-UTR of IL-8 was markedly decreased by miR-520c-3p transfection when compared with scrambled miRNA control transfection (P<0.001). In addition, compared with the scrambled miRNA control transfection, the overexpression of miR-520c-3p significantly reduced the expression of IL-8, and resulted in increased E-cadherin and decreased vimentin and fibronectin levels in MCF-7 and T47D cells (all P<0.001). Introduction of miR-520c-3p inhibited the invasion and migration of MCF-7 and T47D cells (all P<0.001). By contrast, the rescue of IL-8 expression led to the recovery of EMT-related protein expression patterns and cell motility and invasion capabilities. In conclusion, aberrant miR-520c-3p expression may lead to reduced IL-8 expression and promote the mesenchymal phenotype in breast cancer cells, thereby increasing invasive growth.

Different outcomes of never-treated and treated patients with schizophrenia: 14-year follow-up study in rural China.

BACKGROUND: The long-term outcome of never-treated patients with schizophrenia is unclear. AIMS: To compare the 14-year outcomes of never-treated and treated patients with schizophrenia and to establish predictors for never being treated. METHOD: All participants with schizophrenia (n = 510) in Xinjin, Chengdu, China were identified in an epidemiological investigation of 123 572 people and followed up from 1994 to 2008. RESULTS: The results showed that there were 30.6%, 25.0% and 20.4% of patients who received no antipsychotic medication in 1994, 2004 and 2008 respectively. Compared with treated patients, those who were never treated in 2008 were significantly older, had significantly fewer family members, had higher rates of homelessness, death from other causes, being unmarried, living alone, being without a caregiver and poor family attitudes. Partial and complete remission in treated patients (57.3%) was significantly higher than that in the never-treated group (29.8%). Predictors of being in the never-treated group in 2008 encompassed baseline never-treated status, being without a caregiver and poor mental health status in 1994. CONCLUSIONS: Many patients with schizophrenia still do not receive antipsychotic medication in rural areas of China. The 14-year follow-up showed that outcomes for the untreated group were worse. Community-based mental healthcare, health insurance and family intervention are crucial for earlier diagnosis, treatment and rehabilitation in the community.

Risk factors for poor work functioning of persons with schizophrenia in rural China.

BACKGROUND: The long-term work performance of persons with schizophrenia in the community is unclear. This study examined the status of long-term work functioning and the predictors of poor work status among patients with schizophrenia in a Chinese rural area. METHODS: A 10-year follow-up investigation (1994-2004) of a cohort (n = 510) of persons with schizophrenia was conducted in Xinjin County, Chengdu, China. RESULTS: Compared with baseline data, work functioning of patients with schizophrenia deteriorated after 10 years. The rates of not working increased significantly from 12.0% in 1994 to 23.0% in 2004. Bivariate analyses showed that the poor work functioning in 2004 was significantly associated with male gender, older age, older age of first onset, higher level of education, longer duration of illness, lower family economic status, lack of caregivers, poor work status in 1994, living in shabby or unstable house, marked symptoms, and higher score on the Social Disability Screening Schedule (SDSS). In multiple logistic regression analyses, higher score of SDSS and poor work status in 1994 were identified as unique predictors of poor work status in 2004. CONCLUSION: The status of work functioning of persons with schizophrenia decreased over the course of the illness. The risk factors for poor work functioning and specific socio-cultural environment should be considered in planning community mental health services and rehabilitation for these patients.

Criminal behavior among persons with schizophrenia in rural China.

OBJECTIVE: This study is to explore the prevalence and risk factors for self-reported criminal behavior among persons with schizophrenia in rural China. METHODS: We used data from a 14-year prospective follow-up study (1994-2008) of criminal behavior among a cohort (N=510) of persons with schizophrenia in Xinjin County, China. RESULTS: The rate of criminal behavior was 10.0% among persons with schizophrenia in a rural community during the follow-up period. Bivariate analyses showed that the risk of criminal behavior was significantly associated with being male, unmarried, previous violent behavior, homelessness, no family caregivers, and high scores on measures of total symptoms of illness. In multivariate logistic regression analyses being male and previous violent behavior were identified as independent predictors of increased criminal behavior in persons with schizophrenia in the follow-up period. CONCLUSIONS: Criminal behavior is a common phenomenon among patients with schizophrenia in rural China. The findings of the risk factors for criminal behavior should be considered in planning mental health interventions for high-risk patients and their families.

Differences in mortality and suicidal behaviour between treated and never-treated people with schizophrenia in rural China.

BACKGROUND: Many people with schizophrenia remain untreated in the community. Long-term mortality and suicidal behaviour among never-treated individuals with schizophrenia in the community are unknown. AIMS: To explore 10-year mortality and suicidal behaviour among never-treated individuals with schizophrenia. METHOD: We used data from a 10-year prospective follow-up study (1994-2004) among people with schizophrenia in Xinjin County, Chengdu, China. RESULTS: The mortality rate for never-treated individuals with schizophrenia was 2761 per 100 000 person-years during follow-up. There were no significant differences of rates of suicide and all-cause mortality between never-treated and treated individuals. The standardised mortality ratio (SMR) for never-treated people was 10.4 (95% CI 7.2-15.2) and for treated individuals 6.5 (95% CI 5.2-8.5). Compared with treated people, never-treated individuals were more likely to be older, poorer, have a longer duration of illness, marked symptoms and fewer family members. CONCLUSIONS: The never-treated individuals have similar mortality to and a higher proportion of marked symptoms than treated people, which may reflect the poor outcome of the individuals without treatment. The higher rates of mortality, homelessness and never being treated among people with schizophrenia in low- and middle-income nations might challenge presumed wisdom about schizophrenia outcomes in these countries.

Mortality of geriatric and younger patients with schizophrenia in the community.

Little is known about the differences in mortality among non-institutionalized geriatric and younger patients with schizophrenia. In this study long-term mortality and suicidal behavior of all the geriatric (age > or = 65 years), middle-age (age 41-64 years), and young (age 15-40 years) subjects with schizophrenia living in a Chinese rural community were compared. A 10 year follow-up investigation among a 1994 cohort (n = 510) of patients with schizophrenia was conducted in Xinjin County, Chengdu, China. Compared with young subjects, geriatric subjects with schizophrenia were more likely to be female, have more previous physical illness, never accepted treatment, and practice religious (p < or = 0.01). There were no significant differences of suicide attempts among the three groups. Young subjects had a higher rate of suicide (1,033.8 per 100,000 person-years), and geriatric subjects had a higher rate of deaths due to other causes (accident and natural causes) (4,314.2 per 100,000 person-years). Standardized mortality ratios for both suicide and deaths due to other causes were highest in young subjects and the lowest in geriatric subjects. Patients with schizophrenia in all age groups had a marked increase in mortality and suicide. Specific intervention strategies for decreasing mortality and suicide should be developed for patients with schizophrenia in different age groups.