BackgroundThe majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown.MethodslncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment.ResultsWe identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo.ConclusionsOur findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.

According to births in the last year as reported in China's 2000 census, the total fertility rate (TFR) in the year 2000 in China was 1.22 children per woman. This estimate is widely considered to be too low, primarily because some women who had out-of-quota births according to China's one-child family policy did not report those births to the census enumerator. Analysis of fertility trends derived by applying the own-children method of fertility estimation to China's 1990 and 2000 censuses indicates that the true level of the TFR in 2000 was probably between 1.5 and 1.6 children per woman. A decomposition analysis of change in the TFR between 1990 and 2000, based on our best estimate of 1.59 for the TFR in 2000, indicates that about two-fifths of the decline in the conventional TFR between 1990 and 2000 is accounted for by later marriage and less marriage, and three-fifths by declining fertility within marriage. The analysis also applies the birth history reconstruction method of fertility estimation to the two censuses, yielding an alternative set of fertility estimates that are compared with the set derived by the own-children method. The analysis also includes estimates of trends in fertility by urban/rural residence, education, ethnicity, and migration status. Over time, fertility has declined sharply within all categories of these characteristics, indicating that the one-child policy has had large across-the-board effects. Copyright 2005 The Population Council, Inc..

This article examines the contextual effects of community environment on individual stigmatizing attitudes toward people with HIV/AIDS in China. Multilevel logistic regression models are used to analyze data on 5,658 respondents aged 15-49 from 66 communities in the Baseline Information, Education, and Communication Survey for HIV/AIDS Prevention in China, conducted by the State Family Planning Commission in 2000. The results show that a high level of HIV/AIDS-related risk behavior in the community and a low level of community development are associated with increased HIV/AIDS-related stigma, after controlling for respondents' sociodemographic characteristics, including extent of knowledge about HIV/AIDS. The findings suggest that interventions for reducing HIV/AIDS-related stigma in China should take into account community characteristics, such as level of HIV/AIDS-related risk behavior and level of development in the community.

We assessed the MSKCC nomogram performance in predicting SLN metastases in a Chinese breast cancer population. A new model (the SCH nomogram) was developed with clinically relevant variables and possible advantages. Data were collected from 1,545 patients who had a successful SLN biopsy between March 2005 and November 2011. We validated the MSKCC nomogram in the modeling and validation group. Clinical and pathologic features of SLN biopsy in modeling group of 1,000 patients were assessed with multivariable logistic regression to predict the presence of SLN metastasis in breast cancer. The SCH nomogram was created from the logistic regression model and subsequently applied to 545 consecutive SLN biopsies. By multivariate analysis, age, tumor size, tumor location, tumor type, and lymphovascular invasion were identified as independent predictors of SLN metastasis. The SCH nomogram was then developed using the five variables. The new model was accurate and discriminating (with an AUC of 0.7649 in the modeling group) compared to the MSKCC nomogram (with an AUC of 0.7105 in the modeling group). The area under the ROC curve for the SCH nomogram in the validation population is 0.7587. The actual probability trends for the various deciles were comparable to the predicted probabilities. The false-negative rates of the SCH nomogram were 1.67, 3.54, and 8.20 % for the predicted probability cut-off points of 5, 10, and 15 %, respectively. Compared with the MSKCC nomogram, the SCH nomogram has a better AUC with fewer variables and has lower false-negative rates for the low-probability subgroups. The SCH nomogram could serve as a more acceptable clinical tool in preoperative discussions with patients, especially very-low-risk patients. When applied to these patients, the SCH nomogram could be used to safely avoid a SLN procedure. The nomogram should be validated in various patient populations to demonstrate its reproducibility.