Endogenous noncoding circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but their expression pattern in breast cancer has remained largely unknown. In this two-stage study, we first used an Arraystar Human circRNA Array to construct a genome-wide circRNA profile. We then selected candidate circRNAs for validation using a quantitative real-time polymerase chain reaction system. CircRNA/miRNA interactions were predicted and sequence analyses were performed. Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. These circRNAs targeted complementary miRNA response elements. The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.

In recent years, the biological role of changes in physical factors in carcinogenesis and progression has attracted increasing attention. Matrix stiffness, also known as ECM stress, is a critical physical factor of tumor microenvironment and remains alternating during carcinogenesis as a result of ECM remodeling through activation of cancer-associated fibroblasts and extracellular collagen accumulation, crosslinking and fibrosis. Different content and density of extracellular collagen in ECM endows matrix with varying stiffness. Physical signals induced by matrix stiffness are transmitted to tumor cells primarily by the integrins receptor family and trigger a series of mechanotransduction that result in changes in tumor cell morphology, proliferative capacity, and invasive ability. Importantly, accumulating evidence revealed that changes in matrix stiffness in tumor tissues greatly control the sensitivity of tumor cells in response to chemotherapy, radiotherapy, and immunotherapy through integrin signaling, YAP signaling, and related signaling pathways. Here, the present review analyzes the current research advances on matrix stiffness and tumor cell behavior with a view to contributing to tumor cell growth and treatment, with the hope of improving the understanding of the biological role of matrix stiffness in tumors.

BackgroundA variety of abnormalities in vitamin D metabolism have been reported in patients with active tuberculosis. However, intervention trials have produced inconsistent results. We hypothesized that genetic and epigenetic changes in the key genes of the vitamin D metabolic pathway may partly explain the differences between studies.MethodsWe performed a case-control study followed by a prospective cohort study. We recruited 122 patients with pulmonary tuberculosis and 118 healthy controls. The serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were measured. The methylation of the promoter regions of key genes in the vitamin D metabolic pathway (CYP24A1, CYP27A1, CYP27B1, CYP2R1, and VDR) was detected using the Illumina MiSeq platform. The specific methylation profiles were examined as epigenetic biomarkers. The sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to estimate the predictive value of the biomarkers.ResultsThe baseline serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations in the cases were significantly lower than those in the controls (51.60 ± 27.25 nmol/L vs. 117.50 ± 75.50 nmol/L, Z = − 8.515, P < 0.001; 82.63 ± 51.43 pmol/L vs. 94.02 ± 49.26 pmol/L, Z = − 2.165, P = 0.03). We sequenced 310 CpG sites in five candidate genes. After Bonferroni correction, there were 55 differentially methylated CpG sites between cases and controls; 41.5% were in the CYP27B1 gene, 31.7% were in the CYP24A1 gene, 14.7% were in the VDR gene, and 12.3% were in the CYP27A1 gene. When we designated the CpG sites that remained significant after the Bonferroni correction as the biomarkers, the area under the curve (AUC) for the cumulative methylation was 0.810 (95% CI 0.754–0.866). There was an interaction between CYP27A1 methylation level and 1,25-dihydroxyvitamin D concentration associated with the risk of TB (ORinteraction = 4.11, 95% CI 1.26–13.36, P = 0.019). The serum 1,25-dihydroxyvitamin D concentration at the end of the intensive treatment stage was related to a patient’s prognosis (P = 0.008). There were 23 CpG sites that were individually related to the treatment outcomes, but the relationships were not significant after the Bonferroni correction.ConclusionBoth serum vitamin D concentrations and the methylation levels of key genes in the vitamin D metabolic pathway are related to the risk and prognosis of tuberculosis.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0552-6) contains supplementary material, which is available to authorized users.