[Retracted] Exosomal miR­130a­3p promotes the progression of differentiated thyroid cancer by targeting insulin­like growth factor 1.

[This retracts the article DOI: 10.3892/ol.2021.12544.].

miR-4780 Derived from N2-Like Neutrophil Exosome Aggravates Epithelial-Mesenchymal Transition and Angiogenesis in Colorectal Cancer.

Despite significant advances in diagnostic methods and treatment strategies, the prognosis for patients with advanced colon cancer remains poor, and mortality rates are often high due to metastasis. Increasing evidence showed that it is of significant importance to investigate how the tumor microenvironment participates in the development of colorectal cancer (CRC). In this manuscript, neutrophils were sequentially stimulated with all-trans retinoic acid and transforming growth factor-ß in turn to induce the neutrophil polarization. Differentially expressed miRNA in neutrophil exosomes have been sequenced by microarray profile, and the effect of N2-like neutrophil-derived exosomal miR-4780 on epithelial-mesenchymal transition (EMT) and angiogenesis was investigated. In our results, we found that neutrophils were enriched in CRC tumor tissue and that CD11b expression correlated with tumor site and serous membrane invasion. At the same time, we demonstrated that internalization of N2 exosomes exacerbated the viability, migration, and invasion of CRC cell lines and inhibited apoptosis. To further investigate the molecular mechanism, we analyzed the miRNA expression profile in the N2-like neutrophils, which led to the selection of hsa-miR-4780 for the subsequent experiment. The overexpression of miR-4780 from N2-like neutrophil-derived exosomes exacerbated EMT and angiogenesis. Moreover, miR-4780 can regulate its target gene SOX11 to effect EMT and angiogenesis in CRC cell lines. CRC with liver metastasis model also validated that aberrant expression of miR-4780 in N2-like neutrophil exosomes exacerbated tumor metastasis and development of tumor via EMT and angiogenesis. In conclusion, our current findings reveal an important mechanism by which mR-4780 from N2-like neutrophil exosomes exacerbates tumor metastasis and progression via EMT and angiogenesis.

The Effect of Different Nutritional Nursing Support on the Nutritional Status and Disease Recovery of Elderly Patients with Gastrointestinal Tumors during the Perioperative Period.

Objective: This study explored the effect of different nutritional nursing support on nutritional status, immune function, postoperative bowel motility, and complications in elderly patients with gastrointestinal tumors during the perioperative period. Methods: 300 patients with gastrointestinal tumors treated in the Department of Gastroenterology and anorectal surgery of Hangzhou First People's Hospital Affiliated with the Medical College of Zhejiang University from February 2018 to March 2020 were selected as the research objects in this study. Patients were divided into the early enteral nutrition (EEN) and total parenteral nutrition (TPN) groups (150 cases in each group) according to the principle of odd and even admission numbers. The patients in the EEN and TPN groups were given enteral nutrition nursing support and parenteral nutrition nursing support, respectively. The nutritional status, immune function, postoperative bowel motility, and complication rate of the two groups were evaluated 7 days after the operation. Results: The nutritional indexes decreased 3 days after the operation and gradually recovered 7 days after the operation in both groups with different nutritional nursing support. The Hb, TRF, PAB, and ALB indexes in the TPN group were significantly lower than those in the EEN group (P < 0.01). On the 7th day after the operation, the indexes of peripheral blood immunoglobulin (IgG, IgM, and IgA) were significantly lower than those in the TPN group, and T lymphocyte subsets (CD4, CD8, and CD4/CD8) demonstrated that the immunological indexes of patients in the EEN group were significantly higher than those in the TPN group (P < 0.01). In terms of intestinal peristalsis, the time of first exhaust and first defecation in the EEN group was significantly shorter than that in the TPN group (P < 0.01) during the perioperative period. Furthermore, both groups had different degrees of complications, while patients demonstrated a lower complication rate in the EEN group compared to those in the TPN group, suggesting a safer postoperative mode. The results of subgroup analysis showed that the nutritional indexes of the gastric cancer group 7 days after operation were significantly higher than those of the colorectal cancer group under EEN and TPN nutritional support modes. Conclusion: Clinical results have suggested that enteral nutrition nursing support can improve the perioperative nutritional status of elderly patients with gastrointestinal tumors by enhancing the immune function and promoting intestinal peristalsis. Meanwhile, the postoperative EEN mode reduces the rate of complications and demonstrates higher safety. Therefore, it has a high clinical application value.

Long noncoding RNA (lncRNA) HOTAIR: Pathogenic roles and therapeutic opportunities in gastric cancer.

Gastric cancer is one of the first malignant cancers in the world and a large number of people die every year due to this disease. Many genetic and epigenetic risk factors have been identified that play a major role in gastric cancer. HOTAIR is an effective epigenetic agent known as long noncoding RNA (lncRNA). HOTAIR has been described to have biological functions in biochemical and cellular processes through interactions with many factors, leading to genomic stability, proliferation, survival, invasion, migration, metastasis, and drug resistance. In the present article, we reviewed the prognostic value of the molecular mechanisms underlying the HOTAIR regulation and its function in the development of Gastric Cancer, whereas elucidation of HOTAIR-protein and HOTAIR-DNA interactions can be helpful in the identification of cancer processes, leading to the development of potential therapeutic strategies.

Association of RASSF1A Ala133Ser polymorphism with cancer risk: a updated meta-analysis involving 7362 subjects.

It has been demonstrated in many studies that the polymorphism of Ras association domain family 1 isoform A (RASSF1A) is related to tumor risk; however, this conclusion remains a controversy. In this study, we systemically retrieved relevant studies in electronic databases such as PUBMED, and EMBASE, and calculated odds ratios (ORs) as well as relevant 95% confidence intervals (CIs). Besides, meta-package in STATA version 12.0 was used. This meta-analysis finally included altogether 12 studies with 16 case-control articles. According to our data, the polymorphism of RASSF1A Ala133Ser was associated with tumor risk (Ser vs. Ala: OR = 1.68,95% CI = 1.20-2.36; Ala/Ser vs. Ala/Ala:OR = 1.63,95% CI = 1.16-2.27; Ser/Ser vs. Ala/Ala:OR = 3.06,95% CI = 1.91-4.89; Recessive model:OR = 2.67, 95% CI = 1.66-4.32; Dominant model: OR =1.72, 95% CI =1.20-2.45). Further, subgroup analyses stratified based on race and cancer type indicated this polymorphism is related to lung cancer(LC) and hepatocellular carcinoma(HCC) susceptibility in Asians.In conclusion, we found that RASSF1A Ala133Ser polymorphism increased LC and HCC risk in Asians, which requires large-scale, delicately-designed researches for verification.

Correlation Between Components of Malnutrition Diagnosed by Global Leadership Initiative on Malnutrition Criteria and the Clinical Outcomes in Gastric Cancer Patients: A Propensity Score Matching Analysis.

Objective: Malnutrition is recognized as a risk factor for poor outcome in patients with gastric cancer (GC). In 2018, the Global Leadership Initiative on Malnutrition (GLIM) published standardized criteria for the diagnosis of malnutrition. Our aim was to investigate whether any of the components of the GLIM diagnostic criteria were related to worse clinical outcomes in patients with GC. Methods: This study analyzed patients with GC who underwent radical gastrectomy in our hospital between 2014 and 2019. A preoperative nutritional assessment was performed for each patient. Matching was based on the presence of three GLIM components: high weight loss (WL), low body mass index (BMI), and low skeletal muscle index (SMI). Results: The analysis included 1,188 patients, including 241 (20.3%) with high WL, 156 (13.1%) with low BMI, and 355 (29.9%) with low SMI. Before matching, patients who met the GLIM component criteria were mostly associated with older age, low nutritional reserves, and late tumor progression. After matching, the clinical characteristics of the three cohorts were balanced. In the matched queue, the survival prognosis of the high WL group was worse than that of the non-WL group, and the postoperative complication rate was higher in the low SMI group than in the normal SMI group (P <0.05). In addition, the clinical outcomes in the low and normal BMI groups were similar (P >0.05). Conclusion: Of the GLIM criteria, high WL and low SMI may be associated with poor clinical outcomes in patients with GC, while a low BMI may not be associated with outcome.

miR-545 promotes colorectal cancer by inhibiting transferring in the non-normal ferroptosis signaling.

In this study, we examined whether and how miR-545 modulates ferroptosis in colorectal cancer (CRC). HT-29 and HCT-116 human CRC cell viability was examined using a CCK-8 assay and malondialdehyde (MDA) and Fe2+ levels were measured after treatment with the ferroptosis inducers Eradicator of Ras and ST (erastin) and Ras selective lethal 3 (RSL3) with or without miR-545 overexpression or knockdown vectors. Our results demonstrate that miR-545 overexpression inhibited, while miR-545 knockdown further increased, erastin and RSL3-induced upregulation of MDA, reactive oxygen species (ROS), and Fe2+ levels. Similarly, miR-545 overexpression partially reversed, while miR-545 knockdown enhanced, the erastin and RSL3-induced reduction in HT-29 and HCT-116 cell survival rates. Transferrin (TF) was identified as a target gene of miR-545. To determine whether miR-545 suppresses ferroptosis via TF, we overexpressed TF in HT-29 and HCT-116 cells. We found that TF overexpression blocked miR-545-induced changes in ROS, MDA, and Fe2+ levels in HT-29 and HCT-116 cells, thereby inducing CRC cell death. An in vivo assay showed that inhibition of miR-545 decreased tumor growth in nude mice treated with erastin. Together, these findings indicate that miR-545 promotes CRC cell survival by suppressing TF.

Exosomal miR-130a-3p promotes the progression of differentiated thyroid cancer by targeting insulin-like growth factor 1.

The aim of the present study was to determine the expression and diagnostic value of exosomal miR-130a-3p in the serum of patients with differentiated thyroid cancer (DTC). Exosomes were isolated from the serum of patients with DTC and were identified using transmission electron microscopy. A novel exosomal miRNA, miR-130a-3p, was found to be significantly decreased in the serum of patients with DTC compared with those with benign thyroid tumors and healthy controls. Further study revealed that exosomal miR-130a-3p was correlated with the malignant characteristics of DTC, including tumor diameter, lymph node metastasis (LNM) and higher TNM stage. Receiver operating characteristic curve analysis demonstrated that the area under the curve of exosomal miR-130a-3p was better compared with that of TgAb and Tg in patients with DTC. More importantly, the combined use of exosomal miR-130a-3p, TgAb and Tg significantly enhanced the sensitivity and specificity, indicating that exosomal miR-130a-3p is a sensitive biomarker for DTC. A dual luciferase reporter assay indicated that insulin-like growth factor (IGF)-1 was a target gene of miR-130a-3p. Pearson's correlation analysis revealed a negative correlation between serum IGF-1 and serum exosomal miR-130a-3p levels. More importantly, exosomes from patients with DTC increased the expression of IGF-1 and p-PI3K/p-AKT, but these effects were abolished by siRNA targeting IGF-1 in TPC-1 cells. Taken together, the findings of the present study indicated that reduced exosomal miR-130a-3p levels were associated with the risk of DTC and may be used as a biomarker for the diagnosis of DTC.

Extracellular vesicle derived miR-544 downregulates expression of tumor suppressor promyelocytic leukemia zinc finger resulting in increased peritoneal metastasis in gastric cancer.

Peritoneal metastasis (PM) is the main cause of poor prognosis in patients with advanced gastric cancer (GC). Increasing evidence has suggested that cancer-associated EVs in body fluids may assist in the diagnosis and treatment of GC. Here, we investigated the role of GC-derived EVs in PM development. Our results demonstrate that expression of the tumor suppressor promyelocytic leukemia zinc finger (PLZF) is decreased in GC tissues and PM lesions from GC patients. PLZF suppression promoted migration and invasion of peritoneal mesothelial HMrSV5 cells, while PLZF overexpression suppressed HMrSV5 cell migration and invasion. Microarray analysis revealed significantly upregulated expression of several miRNAs in EVs isolated from GC patients with PM, including miR-544. The increased miR-544 expression was confirmed in GC tissues and PM-derived EVs. Transfection with miR-544 reduced PLZF expression in HMrSV5 cells, while miR-544 inhibition increased PLZF expression. Incubation of GC cells with peritoneal mesothelial HMrSV5 cells showed that miR-544 could be transferred from GC-derived EVs to peritoneal cells, where it suppressed the PLZF expression. These findings indicate that EV-mediated transfer of miR-544 decreases the PLZF expression in PM lesions, which suggests miR-544 could potentially serve as a diagnostic biomarker and therapeutic target for treatment of GC patients.

Circulating circRNA Has_Circ_0141633 Serves as a Potential Biomarker for Gastric Cancer.

BACKGROUND: The current study aims to investigate the expression of circRNA has_circ_0141633 in the tissues and serum of patients with gastric cancer (GC). METHODS: RT-qPCR was used to detect the expression of has_circ_0141633 in the tissues and serum of patients with GC. Pearson's correlation was used to analyze the relationship between the level of serum and tissue has_circ_0141633 in GC patients. Receiver characteristic curve (ROC) was used to evaluate the diagnostic value of the expression of serum has_circ_0141633 in GC patients. The relationship between serum has_circ_0141633 and the clinicopathological characteristic was analyzed in GC patients. Kaplan-Meier method was used to analyze the survival rate. RESULTS: The level of serum and tissue has_circ_0141633 in GC patients was significantly higher than that in controls. Pearson's correlation analysis showed a positive correlation between serum and tissue has_circ_0141633 levels (r = 0.846, p < 0.05). ROC curve analysis showed that the AUC of serum has_circ_0141633 was 0.835 (95% CI: 0.753 - 0.916), with the sensitivity and specificity of 84.5% and 93.6%. The level of serum has_circ_0141633 was significantly increased according to the malignant characteristics of tumor diameter, differentiation, lymph node metastasis, and TNM stage. The median survival time of GC patients with low expression of has_circ_0141633 was longer than that of GC patients with high expression of has_circ_0141633. CONCLUSIONS: In summary, upregulation of serum has_circ_0141633 may be expected to be a specific molecular marker for the diagnosis and evaluation of malignant GC.

Long noncoding RNA CCAL promotes gastric cancer cell proliferation and migration in a Myc dependent way.

AIMS: Long non-coding RNAs (lncRNAs) play key roles in cancers, yet their potential molecular mechanisms are not well understood. The objective of this study is to examine the expression, biological functions and mechanism of lncRNA CCAL in gastric cancer (GC). METHODS: MTT and Colony formation assay were used to detect cell proliferation and the colony formation ability of gastric cancer cells. Wound healing, Migration, and invasion assay were respectively used to explore the migration, and invasion in gastric cancer cell lines. Real-time polymerase chain reaction (RT-PCR) was performed to determine the expression level of CCAL. Western Blot was used to determine the expression of related proteins. RESULTS: In the present study, we found that CCAL was upregulated in gastric cancer cell lines. Patients whose tumors had high CCAL expression had a shorter overall survival than patients whose tumors had low CCAL expression. Overexpression CCAL promoted the proliferation, migration and invasion of GC by regulating the expression of myc. CONCLUSION: The present study reveals that CCAL is an oncogenic lncRNA that promotes the tumorigenesis and progression of GC.

LINC00052 Promotes Gastric Cancer Cell Proliferation and Metastasis via Activating the Wnt/ß-Catenin Signaling Pathway.

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. The etiology of GC is complex, and much more attention should be paid to genetic factors. In this study, we explored the role and function of LINC00052 in GC. We applied qRT-PCR and Northern blot to detect the expression of LINC00052 and found it was highly expressed during GC. We also investigated the effects of LINC00052 on tumor prognosis and progression and found that LINC00052 indicated poor prognosis and tumor progression. By performing MTT, colony formation, and Transwell assays, we found that LINC00052 promoted MGC-803 cell proliferation and metastasis. Pull-down and RIP assays showed that LINC00052 could interact with ß-catenin and methyltransferase SMYD2, and immunoprecipitation detection showed that LINC00052 promoted ß-catenin methylation to maintain its stability, so as to activate the Wnt/ß-catenin pathway. Furthermore, XAV939 (inhibitor of ß-catenin) was used to treat MGC-803 cells, and we found that LINC00052 promoted proliferation and metastasis, possibly by activation of the Wnt/ß-catenin pathway. In conclusion, our research demonstrated a carcinogenic role for LINC000052 in GC, which may represent a new approach for the prevention and therapy of this cancer.

Overexpressions of DLL4 and CD105 are Associated with Poor Prognosis of Patients with Pancreatic Ductal Adenocarcinoma.

The aim of this study was to investigate the expression of Delta-like ligand 4(DLL4) and Endoglin(CD105) labeled microvessel density(MVD) in pancreatic ductal adenocarcinoma (PDAC) and evaluate their correlation with major clinicopathologic features and patients' survival. Forty-two pancreatic cancer and 20 normal pancreatic tissues were included in the study. Immunohistochemical staining was employed to assess the expression level of DLL4 both in tumor cells and stromal vascular endothelial cells, as well as CD105 which was used to determine MVD. The relationships of DLL4 and CD105 expression with clinicopathologic parameters and clinical outcome were evaluated. Both DLL4 and CD105-labeled microvessel were observed highly immunostained in PDAC cases, and high expression of DLL4 was positively correlated with MVD. Moreover, the high expression of DLL4 was significantly associated with histological grade, node stage and TNM stage in not only the cancer cells but also stroma; while high expression of CD105 was associated with histological grade, TNM stage, node stage and distant metastasis. In univariant analysis, patients with high expression of DLL4 and CD105 tended to significantly poorer overall survival. Both DLL4 and CD105 were overexpressed in a large proportion of patients with PDAC. The expression of DLL4 was positively correlated with CD105-labeled MVD, indicating DLL4 may involved in angiogenesis. In addition, high DLL4 and CD105 expression correlated with the poor clinical outcome and overall survival in patients with PDAC.

Myelin basic protein induces neuron-specific toxicity by directly damaging the neuronal plasma membrane.

The central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was blocked by acidic lipids and competed by other basic proteins. Further studies revealed that MBP induced damage to neuronal membrane integrity and function by depolarizing the resting membrane potential, increasing the permeability to cations and other molecules, and decreasing the membrane fluidity. At last, artificial liposome vesicle assay showed that MBP directly disturbed acidic lipid bilayer and resulted in increased membrane permeability. These results revealed that MBP induces neurotoxicity through its direct interaction with acidic components on the extracellular surface of neuronal membrane, which may suggest a possible contribution of MBP to the pathogenesis in the CNS disorders with myelin damage.

[Sinonasal teratocarcinosarcoma: a clinical, radiologic and pathologic study of 5 cases].

OBJECTIVE: To study the clinical, radiologic and pathologic features, as well as differential diagnosis of teratocarcinosarcoma in nasal cavity and paranasal sinuses. METHODS: Light microscopic examination and immunohistochemical study was performed in 5 cases of sinonasal teratocarcinosarcoma. The clinical, radiologic and pathologic features were analyzed and the literature was reviewed. RESULTS: All 5 patients were males and their age ranged from 34 to 43 years (mean age = 39 years). The clinical presentation was nasal obstruction, epistaxis and headache. Physical examination often revealed a polypoid mass with contact bleeding. Computed tomography showed a homogeneous nasal mass with obturation of sinuses. Cystic changes, calcification or ossification was not observed. Histologically, the tumor showed a heterogeneous admixture of components from the 3 germ cell layers, exhibiting various degrees of maturation. Squamous epithelium, smooth muscle cells, chondro-osseous tissue, intestinal or respiratory type epithelium, "fetal-type" clear cells and immature neuroepithelium were commonly seen. Immunohistochemical study demonstrated that the epithelial component expressed cytokeratin and epithelial membrane antigen, while the mesenchymal component variably expressed vimentin, smooth muscle actin and S-100 protein. On the other hand, the neuroepithelial component expressed neuron-specific enolase, synaptophysin and chromogranin, and the primitive component expressed CD99. The initial biopsy diagnosis included capillary hemangioma, olfactory neuroblastoma, craniopharyngioma and malignant mixed tumor. Follow-up information was available in all patients. Two of which had local recurrence and 1 had cervical lymph node metastasis. CONCLUSIONS: Sinonasal teratocarcinosarcoma is a rare and highly malignant tumor occurring in sinonasal tract. It manifests mainly in adult males and is characterized by a complex admixture of teratomatous and carcinosarcomatous components. "Fetal-type" clear cells, squamous epithelium and immature neuroepithelium represent important histologic characteristics useful in diagnosis.