Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an enzyme‐free, high‐efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single‐stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in‐depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000‐fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered.

BackgroundAngiogenesis is considered as an important process in the development of malignancies and is associated with cancer progression and metastasis. Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is recognized as a typical angiogenic tumor. Thus, it is of great importance to study the underlying mechanism of angiogenesis in HCC. The long non-coding RNA (lncRNA) ubiquitin conjugating enzyme E2C pseudogene 3 (UBE2CP3) has been reported as an oncogene that promotes tumor metastasis in HCC. However, the role and underlying mechanisms of UBE2CP3 in HCC angiogenesis are still unclear.MethodsWe measured the expression levels of UBE2CP3 by in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in HCC patient samples. We also concomitantly used CD31/PAS double-staining to measure endothelial vessel (EV) density and used qRT-PCR to measure the CD31 mRNA level. HepG2 and SMMC-7721 cells were transfected with Lv-UBE2CP3 or Sh-UBE2CP3 virus to obtain stably over-expressing or knocking-down UBE2CP3 cell lines. The indirect effects of UBE2CP3 on ECs were studied by establishing a co-culture system using Transwell chambers with a 0.4-μm pore size. HCC cells and ECs in the co-culture system were separated, but the cytokines and growth factors were able to communicate with each other. Following exposed to HCC cells, ECs were collected for functional studies. Finally, we studied the function of UBE2CP3 in vivo by chick embryo chorioallantoic membrane (CAM) angiogenesis assays and nude mouse tumorigenicity assays.ResultsIn this study, we found that UBE2CP3 expression was higher in HCC tissues than in para-tumor tissues and was up-regulated in tissues with high EV density. Functionally, we found that in the co-culture systems, HCC cells overexpressing UBE2CP3 promoted HUVEC proliferation, migration and tube formation via the activation of ERK/HIF-1α/p70S6K/VEGFA signalling, increasing the level of VEGFA in HCC cell supernatant. In addition, the opposite results appeared when the expression of UBE2CP3 in HCC cells was knocked down. Consistent with these results, CAM angiogenesis assays and nude mouse tumorigenicity assays showed that UBE2CP3 expression up-regulated EV density in vivo.ConclusionOur study suggests that UBE2CP3 can enhance the interaction between HCC tumor cells and HUVECs and promote HCC tumorigenicity by facilitating angiogenesis.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0727-1) contains supplementary material, which is available to authorized users.

Background The poor outcome of high-grade B-cell lymphoma, with rearrangements of MYC, BCL2 and/or BCL6, also known as double-hit lymphoma or triple-hit lymphoma (DHL or THL), has been well documented, while the clinical significance of extra copies of MYC, BCL2 or BCL6 are still less well known. Methods In total, 130 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) were included in our study. Fluorescence in situ hybridization and immunohistochemistry were performed in all cases to evaluate the genetic status and protein expression levels of MYC, BCL2 and BCL6. Results Among the 130 cases of DLBCL, the prevalence rates of extra copies of MYC, BCL2 and BCL6 were 10.8, 20.0 and 14.6%, respectively, and the corresponding rates of gene rearrangement were 10.0, 14.6 and 16.9%, respectively. In total, 7.7% (10/130) of patients were DHL/THL; 9.2% (12/130) of patients were DLBCL with MYC and BCL2 and/or BCL6 gene abnormalities including rearrangements or extra copies, while excluded DHL/THL. The positive protein expression rates of MYC, BCL2 and BCL6 were 46.9% (61), 75.4% (98) and 70.0% (91), respectively. Among the 51 cases with MYC/BCL2 co-expression, 14 cases showed concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities, and the remaining 37 cases were classified as double-expressor lymphoma (DEL). MYC and BCL2 rearrangement and BCL2 extra copies were all associated with upregulated protein expression. Cases with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities were both associated with MYC/BCL2 co-expression. Patients with concurrence of MYC, BCL2 and/or BCL6 genetic abnormalities excluded DHL/THL had shorter OS ( P < 0.001) than patients with DLBCL with no genetic change, and showed no statistical different with patients with DHL/THL ( P = 0.419). Extra copies of MYC was independent prognostic factors for DLBCL. Conclusions Patients with MYC and BCL2 and/or BCL6 gene extra copies might show a trend towards poor prognosis, and the detection of extra copies of MYC, BCL2 and BCL6 might deserve more attention. Electronic supplementary material The online version of this article (10.1186/s13000-019-0856-7) contains supplementary material, which is available to authorized users.

The inactivation of tumor suppressor gene positive regulatory domain containing I (PRDM1) and activation of signal transducer and activator of transcription 3 (STAT3) have been detected in the majority of extranodal NK/T-cell lymphoma, nasal type (EN-NK/T-NT) cases. In the present study, their association with and effects on the clinicopathologic features of EN-NK/T-NT are described. PRDM1 was revealed to be expressed in 19 out of 58 patients (32.8%) with EN-NK/T-NT, and phosphorylated STAT3 was overexpressed in 42 out of 58 (72.4%). Oncogenic pathways were investigated by NanoString encounter technology in 5 PRDM1(+) and 5 PRDM1(−) EN-NK/T-NT specimens. Multiple oncogenic pathways involved in cell apoptosis, cellcycle (CC) and angiogenesis were discriminately activated in EN-NK/T-NT cases, and in PRDM1(+) cases in particular. The sustained activation of the Janus kinase 3 (JAK)/STAT3 pathway was more pronounced. In addition, missense mutations in the SRC homology 2 domain of STAT3 were detected in 7 out of 37 EN-NK/T-NT cases (18.92%), and the acquired mutation was related to the activation of the JAK3/STAT3 pathway. The downregulation of PRDM1 and upregulation of phospho-STAT3 (Tyr705) were associated with angiocentric infiltration of EN-NK/T-NT (P=0.039). Notably, the prognosis of patients in the PRDM1(+)/STAT3 [mutated (mut-)] group was considerably improved than that of patients in the STAT3(mut+)/PRDM(−) group (P=0.037). In addition, the inhibition of NK/T cell lymphoma cell lines by Stattic and tofacitinib could suppress cell proliferation by inducing cell apoptosis or arresting the CC. The present results revealed that the JAK3/STAT3 oncogenic pathway and PRDM1 expression could stratify clinicopathologic features of EN-NK/T-NT. The inhibition of the JAK3/STAT3 pathway may serve as a treatment option for EN-NK/T-NT.