LncNEN885 inhibits epithelial-mesenchymal transition by partially regulation of Wnt/ß-catenin signalling in gastroenteropancreatic neuroendocrine neoplasms.

It has been shown that long noncoding RNAs (lncRNAs) are involved in the carcinogenesis of multiple cancers. However, the roles of lncRNAs in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remain elusive. In the present study, we found that lncNEN885 was markedly decreased in human gastric NEN samples compared to adjacent normal tissues by transcriptome sequencing. Functionally, silencing or overexpression of lncNEN885 could not obviously affect cell proliferation or apoptosis in BON-1 or LCC-18 cells but could affect cell migration and invasion as well as wound-healing rates. Furthermore, dysregulation of lncNEN885 affected these biological functions by activating epithelial-mesenchymal transition through increased expression of Snail, vimentin, and N-cadherin as well as decreased E-cadherin levels in BON-1 and LCC-18 cells. Silencing of lncNEN885 could dramatically increase the phosphorylation of glycogen synthase kinase-3ß and decrease the expression of adenomatous polyposis coli and Axin, with the subsequent accumulation of ß-catenin. Taken together, dysregulation of lncNEN885 can regulate cell migration and invasion by activating epithelial-mesenchymal transition process partially through canonical Wnt/ß-catenin signaling in GEP-NEN cells, which may be a novel biomarker for the metastasis of GEP-NENs.

Clinical Effect of Tumor-Specific Total Nutrients in Patients with Adjuvant Chemotherapy After Radical Gastric Cancer Resection: A Randomized Controlled Trial.

BACKGROUND: In this study, we combined adjuvant chemotherapy after radical gastric cancer resection with tumor-specific total nutrient therapy to analyze how it affects the nutritional state and immune function of the patient. METHOD: We collected data from 106 patients having undergone adjuvant chemotherapy after radical gastric cancer resection between January 2020 and December 2021. We divided the patients into experimental and control groups (with 53 cases in each group) through single-blinded simple randomization using a random number table and the sealed envelope system. The control group received chemotherapy and the regular nutritional diet at the same time while the experimental group received tumor-specific total nutrients based on the control group. We analyzed the index results for the physical examination, nutritional status, and immune function of the patients in both groups recorded before and after one chemotherapeutic cycle. RESULTS: The control and experimental group compositions were as follows: 58.5% and 52.8% males with a mean age ± standard deviation of 54.36 ± 12.68 and 55.15 ± 12.32 years, respectively. After one chemotherapeutic cycle and the nutritional intervention, the experimental group displayed better physical examination indicators than the control group concerning the weight (55.8 ± 5.41 vs. 54.8 ± 6.94, p = 0.621), body fat mass (13.3 ± 0.88 vs. 13.1 ± 0.91, p = 0.253), upper arm circumference (21.9 ± 0.94 vs. 21.2 ± 1.23 cm, p = 0.001), triceps skinfold thickness (15.1 ± 1.36 vs. 14.3 ± 1.62 cm, p = 0.007), and grip strength (23.0 ± 1.30 vs. 22.3 ± 1.33, p = 0.007). In addition, the experimental group yielded better nutritional-status indicators than the control, including albumin (35.2 ± 1.60 vs. 33.7 ± 1.44 g/L, p = 0.001), hemoglobin (115.7 ± 9.28 vs. 111.5 ± 10.56 g/L, p = 0.032), total protein (63.7 ± 5.85 vs. 60.5 ± 5.27 g/L, p = 0.004), transferrin (2.5 ± 0.53 vs. 2.2 ± 0.58 g/L, p = 0.007), and immune-function indicators CD4+ (32.8 ± 4.82 vs. 28.8 ± 3.76, p = 0.001), CD8+ (34.1 ± 3.36 vs. 37.2 ± 3.85, p = 0.001), CD4/CD8 (1.0 ± 0.28 vs. 0.8 ± 0.34, p = 0.001), IgA (2.7 ± 1.43 vs. 4.1 ± 1.47, p = 0.001), and IgG (8.8 ± 1.74 vs. 10.9 ± 1.28, p = 0.001). CONCLUSION: Combined tumor-specific total nutrient and adjuvant chemotherapy application after radical gastric cancer surgery effectively improves the nutritional state and immune function of the patients and could be applied in clinical practice.

A retrospective study of NENs and miR-224 promotes apoptosis of BON-1 cells by targeting PCSK9 inhibition.

Neuroendocrine neoplasms (NENs) represent relatively rare tumors. The lack of diagnostic, therapeutic method and prognostic factors makes them a challenge to us. We retrospectively reviewed the data of 205 NENs patients among which 157 cases were followed-up. Proprotein convertase subtilisin/kexin 9 (PCSK9), a regulator of low density lipoprotein cholesterol (LDL-C), was confirmed as a target gene of microRNA-224. We found an increased incidence of NENs from 2012 to 2015. Women were usually diagnosed at earlier stages than men (P < 0.05). Tumor grading was associated with primary tumor site, especially esophagus and cardia NENs all at G3 (P <0.001). Age, tumor grading and LDL-C levels were independent risk factors of digestive NENs. Low LDL-C level was significantly correlated with survival rate and median overall survival (OS, P < 0.05). MicroRNA-224 agomir and PCSK9 siRNA could promote apoptosis and suppress proliferation, invasion of BON-1 cells (P < 0.05), but increase the level of glucocorticoid (GC, P < 0.05). Taken together, age, tumor grading and LDL-C level are independent risk factors of NENs. The miR-224/PCSK9/GC axis binds to tumorigenesis and prognosis of pancreatic NENs (p-NENs).

Chromosome region maintenance-1 (CRM1) regulates apoptosis of intestinal epithelial cells via p27kip1 in Crohn's disease.

OBJECTIVE: To investigate the role of chromosome region maintenance-1 (CRM1) in Crohn's disease (CD) and its potential pathological mechanisms. METHODS: The expression and distribution of CRM1 in mucosal biopsies from patients with active CD and normal controls were detected by immunohistochemistry (IHC). We established a murine model of acute colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Western blot was performed to investigate the expression levels of CRM1, apoptotic markers (active caspase-3 and cleaved PARP), p27kip1 and p-p27ser10. IHC was performed to evaluate the distribution of CRM1, and double immunofluorescence (IF) was performed to evaluate the co-localization of CRM1 and active capase-3. Cells of the human intestinal epithelial cell line HT-29 were incubated with tumor necrosis factor-α (TNF-α) to establish an apoptotic in vitro model. Western blot was performed to determine the expression levels of CRM1, active caspase-3, cleaved PARP and p-p27ser10. Cytoplasmic and nuclear extracts were assessed to examine the translocation of CRM1. The interaction between CRM1 and p27kip1 was assessed by co-immunoprecipitation (co-IP) assays. Furthermore, we used small interfering RNA (siRNA) to knock down the protein expression of CRM1 in HT-29 cells and then measured the expression of active caspase-3, cleaved PARP and p-p27ser10. Flow cytometry was used to determine the effect of CRM1 on intestinal epithelial cell (IEC) apoptosis. RESULTS: We observed up-regulation of CRM1 accompanied by elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and p-p27ser10 in IECs of patients with active CD and in TNBS-induced colitis model cells. However, the expression of p27kip1 was negatively correlated with the expression patterns of CRM1, p-p27ser10 and apoptotic biochemical markers. Co-localization of CRM1 and active caspase-3 in IECs of the TNBS group further indicated the possible involvement of CRM1 in IEC apoptosis. By employing TNF-α-treated HT-29 cells as an in vitro IEC apoptosis model, we found that the expression levels of CRM1 and p-p27ser10 were in accordance with active caspase-3 and cleaved PARP. In addition, immunoprecipitation confirmed the physical interaction between CRM1 and p27kip1. siRNA knockdown of CRM1 significantly inhibited the phosphorylation of p27kip1 and the expression of active caspase-3 and cleaved PARP. In addition, flow cytometry analysis also showed that silencing CRM1 by siRNA inhibited TNF-α-induced cellular apoptosis in HT-29 cells. CONCLUSIONS: Up-regulated CRM1 may facilitate IEC apoptosis possibly through p27kip1 in CD, indicating an important role of CRM1 in the pathophysiology of CD.