The role of ANXA1 in the tumor microenvironment.

Annexin A1 (ANXA1) is widely expressed in a variety of body tissues and cells and is also involved in tumor development through multiple pathways. The invasion, metastasis, and immune escape of tumor cells depend on the interaction between tumor cells and their surrounding environment. Research shows that ANXA1 can act on a variety of cells in the tumor microenvironment (TME), and subsequently affect the proliferation, invasion and metastasis of tumors. This article describes the role of ANXA1 in the various components of the tumor microenvironment and its mechanism of action, as well as the existing clinical treatment measures related to ANXA1. These findings provide insight for the further design of strategies targeting ANXA1 for the diagnosis and treatment of malignant tumors.

The effects of doxorubicin loaded aptamer S3-linked DNA tetrahedrons on nasopharyngeal carcinoma.

OBJECTIVE: Our research group in the early stage identified CD109 as the target of aptamer S3 in nasopharyngeal carcinoma (NPC). This study was to use S3 to connect DNA tetrahedron (DT) and load doxorubicin (Dox) onto DT to develop a targeted delivery system, and explore whether S3-DT-Dox can achieve targeted therapy for NPC. METHODS: Aptamer S3-conjugated DT was synthesized and loaded with Dox. The effects of S3-DT-Dox on NPC cells were investigated with laser confocal microscopy, flow cytometry, and MTS assays. A nude mouse tumor model was established from NPC 5-8F cells, and the in vivo anti-tumor activity of S3-DT-Dox was examined by using fluorescent probe labeling and hematoxylin-eosin staining. RESULTS: The synthesized S3-DT had high purity and stability. S3-DT specifically recognized 5-8F cells and NPC tissues in vitro. When the ratio of S3-DT to Dox was 1:20, S3-DT had the best Dox loading efficiency. The drug release rate reached the maximum (0.402 ± 0.029) at 48 h after S3-DT-Dox was prepared and mixed with PBS. S3-DT did not affect Dox toxicity to 5-8F cells, but reduced Dox toxicity to non-target cells. Meanwhile, S3-DT-Dox was able to specifically target the transplanted tumors and inhibit their growth in nude mice, with minor damage to normal tissues. CONCLUSION: Our study highlights the ability and safety of S3-DT-Dox to target NPC cells and inhibit the development NPC.

Magnetic resonance imaging characteristics of brain metastases in small cell lung cancer.

BACKGROUND: Lung is the most common primary site of brain metastases (BMs). For different pathological types of BMs have some similar characteristics, it is still a challenge to confirm the origin based on their characteristics directly. BMs of small cell lung cancer (SCLC) have favorable therapeutic expectations due to their high sensitivity to radiotherapy. This study sought to identify unique characteristics of BMs in SCLC, aiming to assist in clinical decision-making. METHODS: Patients diagnosed with BMs of lung cancer who received radiotherapy from January 2017 to January 2022 were reviewed (N = 284). Definitive diagnosis of BMs of SCLC was reached for 36 patients. All patients underwent head examination using magnetic resonance imaging. The number, size, location, and signal characteristics of lesions were analyzed. RESULTS: There were 7 and 29 patients with single focus and non-single focus, respectively. Ten patients had diffuse lesions, and the remaining 26 patients had a total of 90 lesions. These lesions were divided into three groups according to size: <1, 1-3, and >3 cm (43.33%, 53.34%, and 3.33%, respectively). Sixty-six lesions were located in the supratentorial area, primarily including cortical and subcortical lesions (55.56%) and deep brain lesions (20%). Moreover, 22 lesions were located in the infratentorial area. According to diffusion-weighted imaging and T1-weighted contrast enhancement, the imaging characteristics were classified into six patterns. Hyperintensity in diffusion-weighted imaging and homogeneous enhancement was the most common pattern of BMs in SCLC (46.67%), while partial lesions showed hyperintensity in diffusion-weighted imaging without enhancement (7.78%). CONCLUSIONS: The manifestations of BMs in SCLC were multiple lesions (diameter: 1-3 cm), hyperintensity in diffusion-weighted imaging, and homogeneous enhancement. Interestingly, hyperintensity in diffusion-weighted imaging without enhancement was also one of the characteristics.

Correlation Between Apparent Diffusion Coefficient and the Ki-67 Proliferation Index in Grading Pediatric Glioma.

OBJECTIVE: This study aimed to investigate the correlation between apparent diffusion coefficient (ADC) and the Ki-67 proliferation index with the pathologic grades of pediatric glioma and to compare their diagnostic performance in differentiating grades of pediatric glioma. PATIENTS AND METHODS: Magnetic resonance imaging examinations and histopathologies of 121 surgically treated pediatric gliomas (87 low-grade gliomas [LGGs; grades 1 and 2] and 34 high-grade gliomas [HGGs; grades 3 and 4]) were retrospectively reviewed. The mean tumor ADC (ADCmean), minimum tumor ADC (ADCmin), tumor/normal brain ADC ratio (ADC ratio), and value of the Ki-67 proliferation index of LGGs and HGGs were compared. Correlation coefficients were calculated for ADC parameters and Ki-67 values. The receiver operating characteristic curve was used to determine the diagnostic value of ADCmean, ADCmin, ADC ratio, and Ki-67 proliferation index for differentiating LGGs and HGGs. RESULTS: The ADC values were significantly negatively correlated with glioma grade, and the Ki-67 proliferation index had a significant positive correlation with glioma grade. A significant negative correlation was observed between ADCmean and Ki-67 proliferation index, between ADCmin and Ki-67 proliferation index, and between ADC ratio and Ki-67 proliferation index. The receiver operating characteristic analysis demonstrated moderate to good accuracy for ADCmean in discriminating LGGs from HGGs (area under the curve [AUC], 0.875; sensitivity, 79.3%; specificity, 82.4%; accuracy, 80.2%; positive predictive value [PPV], 92.0%; and negative predictive value [NPV], 60.9% [cutoff value, 1.187] [×10-3 mm2/s]). Minimum tumor ADC showed very good to excellent accuracy with AUC of 0.946, sensitivity of 86.2%, specificity of 94.1%, accuracy of 88.4%, PPV of 97.4%, and NPV of 72.7% (cutoff value, 0.970) (×10-3 mm2/s). The ADC ratio showed moderate to good accuracy with AUC of 0.854, sensitivity of 72.4%, specificity of 88.2%, accuracy of 76.9%, PPV of 94.0%, and NPV of 55.6% (cutoff value, 1.426). For the parameter of the Ki-67 proliferation index, in discriminating LGGs from HGGs, very good to excellent diagnostic accuracy was observed (AUC, 0.962; sensitivity, 94.1%; specificity, 89.7%; accuracy, 90.9%; PPV, 97.5%; and NPV, 78.0% [cutoff value, 7]). CONCLUSIONS: Apparent diffusion coefficient parameters and the Ki-67 proliferation index were significantly correlated with histological grade in pediatric gliomas. Apparent diffusion coefficient was closely correlated with the proliferative potential of pediatric gliomas. In addition, ADCmin showed superior performance compared with ADCmean and ADC ratio in differentiating pediatric glioma grade, with a close diagnostic efficacy to the Ki-67 proliferation index.

NIR-II light evokes DNA cross-linking for chemotherapy and immunogenic cell death.

As a DNA damaging agent, oxaliplatin (OXA) can induce immunogenic cell death (ICD) in tumors to activate the immune system. However, the DNA damage induced by OXA is limited and the ICD effect is not strong enough to enhance anti-tumor efficacy. Here, we propose a strategy to maximize the ICD effect of OXA through the mild hyperthermia generated by nanoparticles with a platinum (IV) prodrug of OXA (Pt(IV)-C16) and a near-infrared-II (NIR-II) photothermal agent IR1061 upon the irradiation of NIR-II light. The mild hyperthermia (43 °C) holds advantages in two aspects: 1) increase the Pt-DNA cross-linking, leading to enhanced DNA damage and apoptosis; 2) induce stronger ICD effects for cancer immunotherapy. We demonstrated that, compared with OXA and photothermal therapy of IR1061 alone, these nanoparticles under NIR-II light irradiation can significantly improve the anti-cancer efficacy against triple-negative breast cancer 4T1 tumor. This new strategy provides an effective way to improve the therapeutic outcome of OXA. STATEMENT OF SIGNIFICANCE: OXA could induce immunogenic cell death (ICD) via stimulating immune responses by increasing tumor cell stress and death, which triggers tumor-specific immune responses to achieve immunotherapy. However, due to the insufficient Pt-DNA crosslinks, the ICD effect triggered by OXA cannot induce robust immune response. Mild hyperthermia has great potential to maximize the therapeutic outcome of oxaliplatin by increasing the Pt-DNA cross-linking to augment the immunoresponse for enhanced cancer immunotherapy.

miR-33b in human cancer: Mechanistic and clinical perspectives.

The microRNAs (miRNAs), an extensive class of small noncoding RNAs (∼22 nucleotides), have been shown to have critical functions in various biological processes during development. miR-33b (or hsa-miR-33b) is down-regulated in cancer of multiple systems. Notably, at least 27 protein-coding genes can be targeted by miR-33b. miR-33b regulates the cell cycle, cell proliferation, various metabolism pathways, epithelial-mesenchymal transition (EMT), cancer cell invasion and migration, etc. In prostate cancer, Cullin 4B (CUL4B) can be recruited to the promoter to inhibit the expression of miR-33b. In gastric cancer, the hypermethylation of the CpG island regulated the expression of miR-33b. Besides, miR-33b could be negatively regulated by 7 competing-endogenous RNAs (ceRNAs), which are all long non-coding RNAs (lncRNAs). There are at least 4 signaling pathways, including NF-κB, MAP8, Notch1, and Wnt/ß-catenin signaling pathways, which could be regulated partially by miR-33b. Additionally, low expression of miR-33b was associated with clinicopathology and prognosis in cancer patients. In addition, the aberrant expression of miR-33b was connected with the resistance of cancer cells to 5 anticancer drugs (cisplatin, docetaxel, bortezomib, paclitaxel, and daunorubicin). Importantly, our work systematically summarizes the aberrant expression of miR-33b in various neoplastic diseases and the effect of its downregulation on the biological behavior of cancer cells. Furthermore, this review focuses on recent advances in understanding the molecular regulation mechanisms of miR-33b. Moreso, the relationship between the miR-33b expression levels and the clinicopathological data and prognosis of tumor patients was summarized for the first time. Overall, we suggest that the current studies of miR-33b are insufficient but provide potential hints and direction for future miR-33b-related research.

Advances in Research on microRNAs Related to the Invasion and Metastasis of Nasopharyngeal Carcinoma.

Nasopharyngeal Carcinoma (NPC), which is associated with latent Epstein-Barr virus infection in most cases, is a unique epithelial malignancy arising from the nasopharyngeal mucosal lining. Accumulating evidence is providing insights into the genetic and molecular aberrations that likely drive nasopharyngeal tumor development and progression. We review recent analyses of microRNAs (miRNAs), including Epstein-Barr virus-encoded miRNAs (EBV-encoded miRNAs) and dysregulated cellular miRNAs, that may be related to the metastasis of nasopharyngeal carcinoma. The studies summarized herein have greatly expanded our knowledge of the molecular biology of NPC involving miRNAs, and they may provide new biological targets for clinical diagnosis and reveal the potential of microRNA therapeutics. However, much remains to be uncovered.

Pediatric dumbbell-shaped orbital schwannoma with extension to the cranial cavity: A case report and literature review.

Orbital schwannomas are rare in children, especially those with intracranial extension. Herein, our report refers to a 12-year-old boy who had a cranial-orbital mass with a dumbbell-like appearance. The total neoplasms was successfully removed via a transcranial approach, and the pathological diagnostic result was schwannoma. Neither radiotherapy nor chemotherapy was performed after surgery, and no recurrences were observed for 3 months. Our report suggests that orbital schwannomas should be differentiated from other types of orbital tumors with sufficient evidence and that complete surgical resection remains the first choice to cure this disease.

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review.

Background and Objective: Annexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help advance the development of novel therapeutic strategies. Hence, this review aims to attract everyone's attention to the important role of ANXA1 in tumors and provide new ideas for clinical tumor treatment. Methods: The PubMed database was mainly used to search for various English research papers and reviews related to the role of ANXA1 in tumors and EMT published from November 1994 to April 2022. The search terms used mainly include ANXA1, EMT, tumor, cancer, carcinoma, and mechanism. Key Content and Findings: This article mainly provides a summary of the roles of ANXA1 and EMT in tumor metastasis as well as the various mechanisms via which ANXA1 facilitates the occurrence of EMT, thereby affecting tumor metastasis. In addition, the expression of ANXA1 in different metastatic tumor cell lines and its roles in tumorigenesis and development are also elaborated. This article has found many tumorous therapeutic targets related to ANXA1 and EMT, further confirming that ANXA1 has a huge potential for the diagnosis, treatment and prognosis of certain cancers. Conclusions: Both the abnormal expression of ANXA1 and the occurrence of EMT are closely related to the invasion and metastasis of tumors, and more interestingly, ANXA1 can impact EMT directly or indirectly by mediating signaling pathways and adhesion among cells. We need more studies to elucidate the effects of ANXA1 on tumor invasion, migration and metastasis through EMT in vitro and in vivo clearly, and ultimately in patients to identify more therapeutic targets.

The rosette-forming glioneuronal tumor mimicked cerebral cysticercosis: a case report.

INTRODUCTION: Rosette-forming glioneuronal tumor (RGNT) is a rare variety of slow growing mixed glioneuronal tumor involving primarily fourth ventricular region. This is a comprehensive analysis of a 22-year-old woman with RGNT composed of mainly cystic components. In addition, the case showed multiple lesions located in brain parenchyma which mimicked cerebral cysticercosis. Here, we analyzed this case and listed some characteristics of RGNTs in reported literature which occurring in atypical locations for further understanding it. CASE REPORT: A 22-year-old woman presented with a history of transient dizziness, nausea, and vomiting. Magnetic resonance imaging (MRI) showed multiple cystic lesions in brain parenchyma and then the patient was diagnosed with cerebral cysticercosis possibility. Empirical anti-infective therapy in addition to a follow-up post 2 weeks of MRI examination showed the lesions unchanged. Finally, a biopsy of the right cerebellar hemisphere lesions verified RGNT. CONCLUSION: RGNT is an uncommon tumor classified as grade I glioma by World Health Organization (WHO) with slightly longer course. The imaging findings of RGNT are not specific especially in atypical areas. RGNT is rare, but we should also consider the possibility in diagnosis and differential diagnosis.

The Diagnostic Value of Apparent Diffusion Coefficient and Proton Magnetic Resonance Spectroscopy in the Grading of Pediatric Gliomas.

OBJECTIVE: The aims of this retrospective study were to assess the value of the quantitative analysis of apparent diffusion coefficient (ADC) and proton magnetic resonance spectroscopy (1H-MRS) metabolites in differentiating grades of pediatric gliomas. PATIENTS AND METHODS: Two hundred and nine pathology-confirmed pediatric gliomas (143 low-grade gliomas [LGGs] and 66 high-grade gliomas [HGGs]) were retrospectively analyzed on preoperative diffusion-weighted magnetic resonance imaging, of which 84 also underwent 1H-MRS. The mean tumor ADC (ADCmean), minimum tumor ADC (ADCmin), tumor/normal brain ADC ratio (ADC ratio), and metabolites (choline/creatine ratio [Cho/Cr], N-acetylaspartate/creatine ratio [NAA/Cr], N-acetylaspartate/choline ratio [NAA/Cho], presence of lactate and lipid peaks) between LGGs and HGGs were analyzed. RESULTS: There were significant negative correlations between the ADC values and glioma grade. Receiver operating characteristic analysis showed that the cutoff ADCmean value of 1.192 × 10-3 mm2/s for the differentiation between low- and high-grade pediatric gliomas provided a sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 77.6%, 80.3%, 78.5%, 89.5% and 62.4%, respectively; the cutoff ADCmin value of 0.973 × 10-3 mm2/s resulted in a sensitivity, specificity, accuracy, PPV, and NPV of 86.0%, 90.9%, 87.6%, 95.3%, and 75.0%, respectively; the cutoff ADC ratio value of 1.384 resulted in a sensitivity, specificity, accuracy, PPV, and NPV of 73.4%, 87.9%, 78.0%, 92.9%, and 60.4%, respectively. A tendency for a positive correlation was found between Cho/Cr and glioma grade. A negative correlation was demonstrated between NAA/Cr or NAA/Cho and glioma grade. Statistical analysis demonstrated a threshold value of 2.601 for Cho/Cr to provide a sensitivity, specificity, accuracy, PPV, and NPV of 81.8%, 51.7%, 71.4%, 76.3%, and 60.0%, respectively, in dividing LGGs and HGGs; a threshold value of 0.705 for NAA/Cr to provide a sensitivity, specificity, accuracy, PPV, and NPV of 76.4%, 75.9%, 76.2%, 85.7%, and 62.9%, respectively; a threshold value of 0.349 for NAA/Cho to provide a sensitivity, specificity, accuracy, PPV, and NPV of 87.3%, 86.2%, 86.9%, 92.3%, and 78.1%, respectively. CONCLUSIONS: The ADC values and metabolites appeared to be significantly correlated to grade in pediatric gliomas. The predictive values may be helpful for preoperative diagnostic predictions.

Annexin A1: A double-edged sword as novel cancer biomarker.

The occurrence, development, infiltration and metastasis of tumors are very complex processes involving the participation of many factors, some of which play a key role. Annexin A1 (ANXA1) is known as an anti-inflammatory protein. However, it has now been recognized to have a broader role beyond the inflammation, including roles in cell proliferation, differentiation, apoptosis, invasion, angiogenesis and metastasis. This review is intended to outline the research surrounding the pathophysiological effects of ANXA1 in tumors and its potential as a therapeutic and diagnostic agent. These studies comprehensively explore the expression changes of ANXA1 in cancer and further explore its mechanism of action in tumors, which is of great clinical significance for the early diagnosis, treatment and prognostic evaluation of tumors.

H19/miR-675-5p Targeting SFN Enhances the Invasion and Metastasis of Nasalpharyngeal Cancer Cells.

AIMS: The aim is to study the role of miR-675-5p coded by long non-coding RNA H19 in the development of Nasopharyngeal Cancer (NPC) and whether miR-675-5p regulates the invasion and metastasis of NPC through targeting SFN (14-3-3σ). The study further validated the relationship between H19, miR-675-5p and SFN in NPC and their relationship with the invasion and metastasis of NPC. METHODS: Western blot was used to detect the expression of 14-3-3σ protein in immortalized normal nasopharyngeal epithelial cells NP69 and different metastatic potential NPC cells, 6-10B and 5-8F. At the same time, to find out the relationship between 14-3-3σ protein and the expression of H19 and miR-675-5p, the expression of H19 and miR-675-5p in normal nasopharynx epithelial cells NP69 and varied nasopharyngeal carcinoma cells 6-10B and 5-8F were quantified by real-time PCR. MiR-675-5p mimic and inhibitor were transfected into NPC 6-10B to over-express and down-express miR-675-5p; miR-675-5p mimic negative control and inhibitor negative control were transfected into NPC 6-10B as control groups. The effect of over-expression and down-expression by miR-675-5p on the expression of 14-3-3σ protein was detected by Western blotting. The 3'-UTR segments of SFN, containing miR-675-5p binding sites were amplified by PCR and the luciferase activity in the transfected cells was assayed to detect whether SFN is the direct target of miR-675-5p. Transwell and scratch assays were used to verify the changes in NPC invasion and metastasis ability of mimics and inhibitors transfected with miR-675-5p. RESULTS: The expression of 14-3-3σ protein in normal nasopharynx epithelial cells NP69 is significantly higher than in varied nasopharyngeal carcinoma cells, 6-10B and 5-8F (P<0.05), and the 14-3-3σ protein levels in low-metastatic nasopharyngeal carcinoma cell 6-10B is higher than in high-metastatic nasopharyngeal carcinoma cell 5-8F. The expression of H19 and miR-675-5p are significantly higher in NPC cells than in NP69 cell (P<0.05). The expression of H19 and miR-675-5p in high-Metastatic nasopharyngeal carcinoma cell 5-8F was higher than in low-Metastatic nasopharyngeal carcinoma cell 6-10B. The expression of 14-3-3σ protein in miR-675-5p mimic cells was significantly lower than in mimic NC (negative control) group and blank control group. However, compared with the blank control group, mimic NC showed no significant difference in 14-3-3σ protein between the two groups. The miR-675-5p inhibitor group was significantly higher than the inhibitor NC group and the blank control group (p<0.05), but there was no significant difference in the expression of 14-3-3σ protein in the inhibitor NC group and the blank control group (p>0.05). Dual-luciferase reporter assay system shows the 3'-UTR segments of SFN containing miR-675-5p binding sites. SFN was the target gene of miR-675-5p. CONCLUSION: 14-3-3σ is downregulated in NPC and is involved in the development of NPC. H19 and miR- 675-5p are upregulated in NPC, which is related to the development of NPC. The over-expression of miR- 675-5p inhibits the expression of 14-3-3σ protein. SFN is the target gene of miR-675-5p. MiR-675-5p targets SFN, downregulates its protein expression and promotes the invasion and metastasis of NPC.

Bioinformatic analysis of differentially expressed genes and identification of key genes in EBV-transformed lymphoblasts.

Although the Epstein-Barr virus (EBV) is a well-known human oncogenic virus, its molecular mechanisms involved in the transformation of healthy human cells remain poorly understood. In this study, human lymphocytes were isolated from the peripheral blood of healthy adults, and lymphocytes were transformed in vitro by EBV. Agilent human whole genome microarrays were used to detect the differential gene expression profiles of EBV-transformed lymphoblasts and healthy peripheral blood lymphocytes (PBLs). By constructing the gene functional network of EBV-induced lymphocyte transformation, we screened out candidate key genes in this process and verified their expression levels by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. In the EBV-transformed lymphoblasts, 2335 differentially expressed genes, including 1328 up-regulated and 1007 down-regulated, were screened out. Five candidate key genes, namely, PLK1, E2F1, PTPN11, BIRC5 and FYN were mainly screened out according to the results of LIMMA, String, Cytoscape software analysis. RT-qPCR and Western blot showed that PLK1, E2F1, PTPN11, BIRC5 genes had increased expression levels, and FYN gene was down-regulated in EBV-transformed lymphoblasts. Silencing of PLK1 gene in Raji cells could inhibit cell proliferation and invasion, and induce cell cycle arrest and apoptosis. In conclusion, PLK1, E2F1, PTPN11, BIRC5 and FYN are the candidate key molecules of EBV-transformed lymphocytes.

The Value of 1H-MRS and MRI in Combined Methylmalonic Aciduria and Homocystinuria.

OBJECTIVE: The aims of this study were to describe the brain magnetic resonance imaging (MRI) features of methylmalonic aciduria and homocystinuria and to evaluate the additional value of H-MRS. PATIENTS AND METHODS: Twenty-eight children with methylmalonic aciduria and homocystinuria were included in this study. The control group included 21 healthy children. All the cases underwent MRI and H-MRS before treatment. We measured the N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and myoinositol (mI) peaks in the basal ganglia regions. The NAA/Cr, Cho/Cr, mI/Cr, and NAA/Cho ratios were calculated. We also observed whether there were lactic acid peaks. RESULT: We identified that NAA/Cr and NAA/Cho significantly decreased in the basal ganglia and that 3 patients showed lactate peaks, but other metabolites were not significantly altered. Hydrocephalus and diffuse supratentorial white matter edema were the primary MR findings; 7 patients had thinning of the corpus callosum, and 2 patients had subdural hematoma. Six patients showed normal brain MRI findings. CONCLUSIONS: Methylmalonic aciduria and homocystinuria patients with metabolite changes in the basal ganglia demonstrate compromised neuronal integrity, and anerobic metabolism occurs in acute encephalopathic episodes. H-MRS is a useful tool for evaluating brain damage. Hydrocephalus and diffuse supratentorial white matter edema are the main MRI features.

MiR-597 Targeting 14-3-3σ Enhances Cellular Invasion and EMT in Nasopharyngeal Carcinoma Cells.

BACKGROUND: Alterations in microRNAs (miRNAs) are related to the occurrence of nasopharyngeal carcinoma (NPC) and play an important role in the molecular mechanism of NPC. Our previous studies show low expression of 14-3-3σ (SFN) is related to the metastasis and differentiation of NPC, but the underlying molecular mechanisms remain unclear. METHODS: Through bioinformatics analysis, we find miR-597 is the preferred target miRNA of 14-3-3σ. The expression level of 14-3-3σ in NPC cell lines was detected by Western blotting. The expression of miR-597 in NPC cell lines was detected by qRT-PCR. We transfected miR-597 mimic, miR-597 inhibitor and 14-3-3σ siRNA into 6-10B cells and then verified the expression of 14-3-3σ and EMT related proteins, including E-cadherin, N-cadherin and Vimentin by western blotting. The changes of migration and invasion ability of NPC cell lines before and after transfected were determined by wound healing assay and Transwell assay. RESULTS: miR-597 expression was upregulated in NPC cell lines and repaired in related NPC cell lines, which exhibit a potent tumor-forming effect. After inhibiting the miR-597 expression, its effect on NPC cell line was obviously decreased. Moreover, 14-3-3σ acts as a tumor suppressor gene and its expression in NPC cell lines is negatively correlated with miR-597. Here 14-3-3σ was identified as a downstream target gene of miR-597, and its downregulation by miR-597 drives epithelial-mesenchymal transition (EMT) and promotes the migration and invasion of NPC. CONCLUSION: Based on these findings, our study will provide theoretical and experimental evidences for molecular targeted therapy of NPC.

MRI and clinical features of maple syrup urine disease: preliminary results in 10 cases.

PURPOSE: We aimed to evaluate the magnetic resonance imaging (MRI) and clinical features of maple syrup urine disease (MSUD). METHODS: This retrospective study consisted of 10 MSUD patients confirmed by genetic testing. All patients underwent brain MRI. Phenotype, genotype, and areas of brain injury on MRI were retrospectively reviewed. RESULTS: Six patients (60%) had the classic form of MSUD with BCKDHB mutation, three patients (30%) had the intermittent form (two with BCKDHA mutations and one with DBT mutation), and one patient (10%) had the thiamine-responsive form with DBT mutation. On diffusion-weighted imaging, nine cases presented restricted diffusion in myelinated areas, and one intermittent case with DBT mutation was normal. The classic form of MSUD involved the basal ganglia in six cases; the cerebellum, mesencephalon, pons, and supratentorial area in five cases; and the thalamus in four cases, respectively. The intermittent form involved the cerebellum, pons, and supratentorial area in two cases. The thiamine-responsive form involved the basal ganglia and supratentorial area. CONCLUSION: Our preliminary results indicate that patients with MSUD presented more commonly in classic form with BCKDHB mutation and displayed extensive brain injury on MRI.

Annexin A1 can inhibit the in vitro invasive ability of nasopharyngeal carcinoma cells possibly through Annexin A1/S100A9/Vimentin interaction.

Annexin A1 is a member of a large superfamily of glucocorticoid-regulated, calcium- and phospholipid-binding proteins. Our previous studies have shown that the abnormal expression of Annexin A1 is related to the occurrence and development of nasopharyngeal carcinoma (NPC). To understand the roles of Annexin A1 in the tumorigenesis of NPC, targeted proteomic analysis was performed on Annexin A1-associated proteins from NPC cells. We identified 436 proteins associated with Annexin A1, as well as two Annexin A1-interacted key proteins, S100A9 and Vimentin, which were confirmed by co-immunoprecipitation. Gene function classification revealed that the Annexin A1-associated proteins can be grouped into 21 clusters based on their molecular functions. Protein-protein interaction analysis indicated that Annexin A1 /S100A9/Vimentin interactions may be involved in the invasion and metastasis of NPC because they can form complexes in NPC cells. The down-regulation of Annexin A1 in NPC may lead to the overexpression of S100A9/Vimentin, which may increase the possibility of the invasion ability of NPC cells by adjusting the function of cytoskeleton proteins. Results suggested that the biological functions of Annexin A1 in NPC were diverse, and that Annexin A1 can inhibit the in vitro invasive ability of NPC cells through Annexin A1 /S100A9/Vimentin interaction.

Downregulation of Annexin A1 is correlated with radioresistance in nasopharyngeal carcinoma.

Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance often remains an obstacle to successful treatment. In our previous study, it was demonstrated that Annexin A1 (ANXA1) was involved in the p53-mediated radioresponse in NPC cells, which suggested that it may be associated with radioresistance in NPC; however, the role of ANXA1 in NPC radioresistance is unknown. In the present study, CNE2 cells were stably transfected with pLKO.1-ANXA1-small hairpin (sh)RNAs to investigate the effects of ANXA1 on the radiosensitivity of NPC. CNE2 cells transfected with pLKO.1 were used as the control. The radiosensitivities of the cells in vitro were analyzed using the clonogenic survival assay, cell growth analysis, flow cytometry and Hoechst 33258 staining. ANXA1 downregulation significantly enhanced clonogenic survival and cell growth following treatment of CNE2 cells with ionizing radiation (IR), increased the number of cells in the S phase and decreased IR-induced apoptosis. These results suggested that the radiosensitivity of CNE2 cells transfected with ANXA1-specific shRNA was significantly lower compared with the control cells. Therefore, ANXA1 downregulation may be involved in the radioresistance of NPC, and ANXA1 may be considered a novel biomarker for predicting NPC response to radiotherapy.

Expression of the Annexin A1 gene is associated with suppression of growth, invasion and metastasis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) has a highly increased incidence rate (20/100,000) in Southern regions of China, while being rare in the rest of the world. NPC is a malignant type of cancer due to its high occurrence rate of metastasis; however, biomarkers for effective diagnosis and treatment are yet to be identified. Annexin A1 is a glucocorticoid­regulated member of a large superfamily of calcium and phospholipid­binding proteins and has been shown to have important roles in tumor development and progression, and was demonstrated to be a prognostic biomarker for head and neck cancer types. A previous study by our group showed that Annexin A1 was decreased in NPC tissue as compared with normal adjacent tissue. To investigate whether Annexin A1 is a potential biomarker for NPC, the present study assessed the effect of the Annexin A1 on the biological behavior (i.e., invasion and metastasis) of the highly metastatic NPC cell line 5­8F and the non­metastatic NPC cell line 6­10B. The expression levels of Annexin A1 in the above two cell lines were determined by western blot analysis. Next, the recombinant plasmid pEGFP­C1­Annexin A1 and the small interfering (si)RNA plasmid pRNAT­U6.1­Annexin A1 were used and stably transfected into 5­8F and 6­10B cells, respectively. These established recombinant cell lines were then used to study the up- and downregulation of Annexin A1, respectively. The correlation of Annexin A1 expression levels with the biological behavior of NPC cell lines was analyzed using a cell proliferation assay, flow cytometry, soft agar colony formation assay, as well as Transwell invasion and migration assays. The results demonstrated that upregulation of Annexin A1 suppressed the proliferation, invasion and migration of NPC cells, while downregulation of Annexin A1 promoted the proliferation, invasion and migration of NPC cells. These findings suggested that Annexin A1 may be a potential biomarker for the development and prognosis of NPC, and its dysregulation may have an important role in its underlying pathogenesis.