BackgroundAccumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC.MethodsQuantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1.ResultsHere we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it.ConclusionsOur results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0873-2) contains supplementary material, which is available to authorized users.

BackgroundEmerging evidence has shown long noncoding RNAs (lncRNAs) exert important roles in colorectal cancer (CRC) tumorigenesis. However, most lncRNAs involved in this process remain undefined and the underlying molecular mechanisms mediated by lncRNAs are largely unknown.MethodsAn unbiased screening was used to identify novel lncRNAs involved in CRC according to an online-available data dataset. In situ hybridization (ISH) and qRT-PCR was used to detect lncRNA expression patterns. CCK8, colony formation, fluorescence activated cell sorter (FACS), transwell, xenograft nude mouse model and western blot assays were used to analyze the functions of SLCO4A1-AS1. RNA-pulldown, western blot, RNA fluorescence in situ hybridization (RNA-FISH) and electrophoretic mobility shift assay (EMSA) assays were utilized to explore the molecular mechanism of SLCO4A1-AS1.ResultsLncRNA SLCO4A1-AS1 was significantly upregulated in CRC tissues and its overexpression was closely related with poor prognosis and tumor metastasis. By knocking down SLCO4A1-AS1, we found that SLCO4A1-AS1 promoted the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of CRC cells in vitro, as well as inhibited cell apoptosis. Moreover, SLCO4A1-AS1 dramatically delayed tumor propagation in vivo. Mechanistically, SLCO4A1-AS1 activates Wnt/β-catenin signaling. SLCO4A1-AS1 enhanced the stability of β-catenin by impairing the interaction of β-catenin with GSKβ and inhibiting its phosphorylation. Finally, restoration of β-catenin protein level rescued the proliferation, migration and invasion in SLCO4A1-AS1-depleted CRC cells.ConclusionSLCO4A1-AS1 serves as an oncogenic role in CRC through activating Wnt/β-catenin signaling pathway. And SLCO4A1-AS1 might be a useful biomarker for CRC diagnosis and prognosis.

Thymidine kinase 1 (TK1) is a pyrimidine metabolic pathway enzyme involved in salvage DNA synthesis and thus, a cell cycle-dependent marker. We have developed anti-TK1 monoclonal/polyclonal Abs raised against a 15-amino acid synthetic peptide (KPGEAVAARKLFAPQ) corresponding to part of the C-terminus of human TK1. These Abs are useful for both serological and immunohistochemical detection of TK1 in a number of cancer diseases. In this study we examined TK1 concentration in serum (STK1) in 250 preoperative non-small cell lung cancer patients (NSCLC), including 188 non-metastatic (group M0) and 62 metastatic patients (group M1). Serum from 16 healthy individuals was used as controls. The concentration of STK1 of preoperative NSCLC patients was significantly higher than STK1 of healthy individuals (p<0.0001). In group M0, preoperative STK1 concentration was significantly higher in patients of tumour size T2, as compared to tumour size T1 (p=0.042), and in T3-T4, as compared to T1-T2 (p=0.01). No significant difference in STK1 concentration between patients of tumour stage I and stage II (p=0.057) were found, but significantly higher STK1 concentration in patients of stage III, as compared stage I-II (p=0.025). No significant difference of STK1 concentration were found in patients of group M1 concerning tumour size or tumour stage, or between patients with adenocarcinomas (AC) and squamous cell carcinomas (SCC). We studied the changes of STK1 concentration individually one month after operation in metastatic subjects (group M1, n=19) and in tumour-free subjects (group M0, n=38). In the M0 group, the concentration of STK1 one month after operation was significantly decline by 45%, when comparing to concentrations of STK1 preoperative (p<0.001). In the group M1, however, no significant decrease in STK1 concentrations were found one month after operation. We conclude that STK1 has prognostic value and is a reliable marker for monitoring the response to surgery of NSCLC patients.

Vascular smooth muscle cell (VSMC) proliferation and migration are vital to atherosclerosis (AS) development and plaque rupture. MicroRNA-377-3p (miR-377-3p) has been reported to inhibit AS in apolipoprotein E knockout (ApoE−/−) mice. Herein, the mechanism underlying the effect of miR-377-3p on alleviating AS is explored. In vivo experiments, ApoE−/− mice were fed with high-fat diet (HFD) to induce AS and treated with miR-377-3p agomir or negative control agomir (agomir-NC) on week 0, 2, 4, 6, 8, 10 after HFD feeding. MiR-377-3p was found to restore HFD-induced AS lesions and expressions of matrix metalloproteinase (MMP)-2, MMP-9, α-smooth muscle actin (α-actin) and calponin. In in vitro experiments, human VSMCs were tranfected with miR-377-3p agomir or agomir-NC, followed by treatment with oxidized low-density lipoprotein (ox-LDL). MiR-377-3p was observed to significantly inhibit ox-LDL-induced VSMC proliferation characterized by inhibited cell viability, expressions of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E and cell cycle transition from G1 to S phase accompanied with less 5-Ethynyl-2′-deoxyuridine (EdU)-positive cells. Furthermore, MiR-377-3p significantly inhibited ox-LDL-induced VSMC migration characterized by inhibited wound closure and decreased relative VSMC migration. Besides, neuropilin2 (NRP2) was verified as a target of miR-377-3p. MiR-377-3p was observed to inhibit NRP2 expressions in vivo and in vitro. Moreover, miR-377-3p significantly inhibited MMP-2 and MMP-9 expressions in human VSMCs. Additionally, miR-377-3p-induced inhibition of VSMC proliferation and migration could be attenuated by NRP2 overexpression. These results indicated that miR-377-3p inhibited VSMC proliferation and migration via targeting NRP2. The present study provides an underlying mechanism for miR-377-3p-based AS therapy.

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BackgroundThis study evaluates the feasibility and strategy of left tracheobronchial lymph node (LN) dissection in the surgical treatment of esophageal cancer, and its impact on surgical outcomes following thoracoscopic esophagectomy.MethodsData of 265 patients with thoracic esophageal cancer who underwent thoracoscopic and laparoscopic esophagectomy was retrospectively reviewed. In 80 cases, thoracoscopic esophagectomy was performed without left tracheobronchial LN dissection (group non‐4L), while 185 cases underwent thoracoscopic esophageal mobilization with routine left tracheobronchial node dissection (group 4L). We introduced a “mesoesophageal suspension” method in order to facilitate complete dissection of the left tracheobronchial nodes, along with left recurrent laryngeal nerve nodes. Both univariate and multivariate analyses were performed to evaluate risk factors correlated to left tracheobronchial node metastasis.ResultsThe non‐4L group experienced less blood loss than the 4L group (P = 0.009). More mediastinal LNs were dissected in the 4L group (P < 0.001). There was no significant difference with regard to the incidence of major postoperative complications between the two groups. Compared with other LN metastases, the metastatic rate of the left tracheobronchial LNs was relatively lower. Based on multivariate analysis of six factors, lymphatic invasion and subcarinal node metastasis were shown to be strong independent predictors of left tracheobronchial metastasis.ConclusionRoutine thoracoscopic extensive lymphadenectomy, including the left tracheobronchial LN, was technically feasible and safe in patients with esophageal cancer. Using a mesoesophagus suspension technique, we performed a meticulous LN dissection in the upper mediastinal space.

We report here a new structure, named`strings-ofpearls', which are seen to form in Xenopus egg extracts after incubation, as 200 nm membrane vesicles attach to 10 nm filaments. These membrane vesicles fuse together along the filaments to form annulate lamellae (AL) or attach to demembranated sperm chromatin to initiate assembly of a nuclear envelope. Immunoassay with anti-keratin antibodies AE3 showed that the filaments were mainly composed of a 56 kDa keratin-like protein. Addition of AE3 to the extracts resulted in inhibition of AL formation and defective assembly of NE. These results suggest a function of keratins in the assembly of nuclear envelopes during Xenopus development.z 1998 Federation of European Biochemical Societies.

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