Although there are some studies to investigate germline mutations in BRCA1/2 genes in Chinese women with familial breast cancer, many of them suffer relatively small sample size. In this study, we screened germline mutations in BRCA1/2 genes in a cohort of 409 Chinese women with familial breast cancer from north China by using a PCR-sequencing assay. A total of 43 deleterious mutations in BRCA1/2 genes were identified in this cohort, including 17 novel mutations and 6 recurrent mutations. The frequencies of BRCA1 and BRCA2 mutations were 3.9% (16/409) and 6.6% (27/409), respectively; the mutation rate of BRCA2 was 1.7-fold higher than that of BRCA1. The entire mutation rate of BRCA1/2 was 10.5% in this cohort; however, the mutation rate of BRCA1/2 genes was 23.0% in 78 familial breast cancer patients whose tumors were diagnosed at or before the age of 40. The mean age at diagnosis of breast cancer in BRCA1 carriers (42.8 years) and BRCA2 carriers (45.1 years) was younger than non-carriers (51.0 years) in this cohort (P = 0.005; P = 0.01, respectively). In addition, both BRCA1 carriers and BRCA2 carriers were more likely to exhibit triple-negative breast cancer (ER-, PgR-, and HER2-) than non-carriers (BRCA1 carriers vs. non-carriers, 69.2 vs. 23.0%, P = 0.001; BRCA2 carriers vs. non-carriers, 45.8 vs. 23.0%, P = 0.01). Our study suggested that the spectrum and characteristics of BRCA1/2 mutations in Chinese familial breast cancer exhibit some unique features, and Chinese women with familial breast cancer whose tumors are diagnosed at or before the age of 40 are good candidates for BRCA1/2 testing.

BackgroundSUMO-activating enzyme subunit 2 (SAE2) is the sole E1-activating enzyme required for numerous important protein SUMOylation, abnormal of which is associated with carcinogenesis. SAE2 inactivation was recently reported to be a therapeutic strategy in cancers with Myc overexpression. However, the roles of SAE2 in small cell lung cancer (SCLC) are largely unknown.MethodsStably SAE2 knockdown in H446 cells were established with a lentiviral system. Cell viability, cell cycle, and apoptosis were analyzed using MTT assay and flow cytometric assay. Expression of SAE2 mRNA and protein were detected by qPCR, western blotting, and immunohistochemical staining. Cell invasion and migration assay were determined by transwell chamber assay. H446 cells with or without SAE2 knockdown, nude mice models were established to observe tumorigenesis.ResultsSAE2 was highly expressed in SCLC and significantly correlated with tumorigenesis in vivo. Cancer cells with RNAi-mediated reduction of SAE2 expression exhibited growth retardation and apoptosis increasing. Furthermore, down-regulation of SAE2 expression inhibited migration and invasion, simultaneously increased the sensitivity of H446 to etoposide and cisplatin.ConclusionsSAE2 plays an important role in tumor growth, metastasis, and chemotherapy sensitivity of H446 and is a potential clinical biomarker and therapeutic target in SCLC with high c-Myc expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0164-y) contains supplementary material, which is available to authorized users.

BackgroundmiRNAs are a class of small non-coding RNA molecules that play an important role in the pathogenesis of human diseases through negative regulation of gene expression. Although miRNA-10b (miR-10b) has been implicated in other tumors, its role in non-small cell lung cancer (NSCLC) is still unknown. The aim of the present study was to investigate the role of miR-10b in NSCLC.MethodsExpression of miR-10b was analyzed in NSCLC cell line A549 by qRT-PCR. Cell viability was evaluated using Cell Counting Kit (CCK)-8. Cell migration and invasion were evaluated by wound healing assay and transwell assays. Cell cycle and apoptosis analyses were performed. Western blotting was used to predicate the target of miR-10b.ResultsThe A549 cell line transfected with the miR-10b exhibited significantly increased proliferation, migration, and invasion capacities when compared with the control cells (P < 0.05). Krüppel-like factor 4 (KLF4) may be indirectly targeted by miR-10b during the proliferation increasing of A549 cells.ConclusionIn this study, we found that miR-10b is a tumor enhancer in NSCLC. Thus, miR-10b may represent a potential therapeutic target for NSCLC intervention.

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Cell cultures are used in pharmaceutical, medical and biological sciences. Due to the ethical and cost limitations of in vivo models, the replaceable cell model that is more closely related to the characteristics of organisms, which has broad prospects and can be used for high-throughput drug screening is urgent. Neuronal and glial cell models have been widely used in the researches of neurological disorders. And the current researches on neuroinflammation contributes to blood-brain barrier (BBB) damage. In this review, we describe the features of healthy and inflamed BBB and summarize the main immortalized cell lines of the central nervous system (PC12, SH-SY5Y, BV2, HA, and HBMEC et al.) and their use in the anti-inflammatory potential of neurological disorders. Especially, different co-culture models of neuroinflammatory, in association with immune cells in both 2D and 3D models are discussed in this review. In summary, 2D co-culture is easily practicable and economical but cannot fully reproduce the microenvironment in vivo. While 3D models called organs-on-chips or biochips are the most recent and very promising approach, which made possible by bioengineering and biotechnological improvements and more accurately mimic the BBB microenvironment.