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Oncogenic fusion gene Echinoderm Microtubule-associated protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) contributes to tumorigenesis of a subset of non-small cell lung cancer (NSCLC). Recently, we demonstrated that F-circEA-4a, a tumor-promoting circular RNA (circRNA) generated from the back-splicing of EML4-ALK variant 3b (v3b), is a novel liquid biopsy biomarker for NSCLC. However, circRNAs produced from EML4-ALK gene and their roles in NSCLC are not well-characterized. Here, we identify another EML4-ALK-v3b-derived circRNA, F-circEA-2a, harboring “AA” (rather than “AAAA” in F-circEA-4a) motif at the junction site. F-circEA-2a mainly locates in the cytoplasm and promotes cell migration and invasion, but has little effect on cell proliferation. Moreover, F-circEA-2a exists in tumor, but not in the plasma of NSCLC patients with EML4-ALK fusion gene, further supporting the significant diagnostic value of F-circEA-4a for EML4-ALK-positive NSCLC. This work finds a novel oncogenic circRNA generated from EML4-ALK fusion gene, highlighting the pivotal role of circRNA in EML4-ALK-positive NSCLC development.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0887-9) contains supplementary material, which is available to authorized users.

Long noncoding RNAs (lncRNA) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here, we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell-cycle arrest and tumor growth inhibition and, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. These findings identify a tumor-suppressive long noncoding RNA in papillary thyroid carcinoma. http://cancerres.aacrjournals.org/content/canres/78/15/4163/F1.large.jpg .

We sequenced a 705-bp fragment of the recA gene from 113 Vibrio cholerae strains and closely related species. One hundred eighty-seven nucleotides were phylogenetically informative, 55 were phylogenetically uninformative, and 463 were invariant. Not unexpectedly, Vibrio parahaemolyticus and Vibrio vulnificus strains formed out-groups; we also identified isolates which resembled V. cholerae biochemically but which did not cluster with V. cholerae. In many instances, V. cholerae serogroup designations did not correlate with phylogeny, as reflected by recA sequence divergence. This observation is consistent with the idea that there is horizontal transfer of O-antigen biosynthesis genes among V. cholerae strains.Understanding the transfer of genes within and among bacteria requires knowledge of the genetic relatedness of the bacteria. Pandemic strains of Vibrio cholerae have acquired the major virulence factors cholera toxin and toxin-coregulated pilus (TCP) by lysogeny (14,27). The recent appearance of the O139 epidemic strain of V. cholerae probably occurred via acquisition of a new surface polysaccharide through a horizontal gene transfer event (5,8,23). In order to better understand this event and in hopes of predicting future events, we have begun to generate multilocus sequencing (MLS) genotypes of various strains of V. cholerae. MLS has three advantages over multilocus enzyme electrophoresis: (i) MLS detects more variation for each locus (e.g., silent substitutions), (ii) convergence of alleles is less likely, and (iii) MLS data are easily compared across laboratories (16). Sequencing of aldA and the cholera toxin genes, ctxA and ctxB, has proven useful in studying the epidemiology of pandemic strains but is limited to toxigenic isolates (12,26). Sequencing the asd gene has broader application but has been done for only 24 non-O1 isolates (13). Studies using the pattern of IS1004 insertions and pulsed-field gel electrophoresis (PFGE) have also looked at only limited numbers of non-O1 V. cholerae isolates (5, 6).In this brief communication, we report our results from sequencing a 705-bp fragment of the recA gene from 107 strains that had initially been designated V. cholerae and 5 strains of other Vibrio species. The locus chosen for study was recA because it has been shown to be useful for estimating phylogeny, in contrast to some other genes (9). Strains are listed in Table 1; strains are from our collection at the University of Maryland and include strains representative of known outbreaks, as well as serogroup type strains from the Smith Vibrio Reference Laboratory collection (22) of non-O1 V. cholerae.Minipreparations of chromosomal DNA were made from each strain using the Wizard genomic DNA purification kit (Promega). DNAs were diluted to 10 ng/l, and 1 l was used for PCR amplification of the recA gene. The base sequence from 813 to 1598 (numbering based on the V. cholerae sequence, GenBank accession no. X71969) of the recA gene was determined in two directions from PCR products using cycle sequencing an...

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Studies have showed that dysfunction in the breast cancer susceptibility gene (BRCA) is associated with triple-negative breast cancer (TNBC); however, its effect on patient survival remains controversial. We investigated the distribution of BRCA1/2 mutations in unselected Chinese patients with TNBC and explored their roles in prognosis. Then a systematic review and meta-analysis were performed to evaluate the prognostic role of BRCA dysfunction, including BRCA1/2 germline/somatic mutations, BRCA1 promoter methylation, and low BRCA1 protein expression in TNBC patients. Pooled hazard ratios with 95% confidence intervals were estimated to determine the association between BRCA dysfunction and survival. Our results showed a high frequency of BRCA1/2 mutations, especially germline BRCA1 variants, were associated with bilateral breast cancer. Although no correlations were found between BRCA1/2 mutations and recurrence-free survival (RFS) or overall survival (OS). In the meta-analysis, patients with BRCA1 promoter methylation showed poor OS. However, there was a favorable impact on disease free survival (DFS) for TNBC patients with BRCA1 promoter methylation when received adjuvant-chemotherapy. In conclusion, BRCA1/2 mutations were associated with bilateral breast cancer and BRCA1 promoter methylation may have a prognostic effect on TNBC.