CIC::NUTM1 sarcomas occurred in soft tissues of upper limbs : a rare case report and literature review.

BACKGROUND: CIC-rearranged sarcomas (CRS) represent a new entity of undifferentiated small round cell sarcoma belonging to the Ewing-like sarcomas family. CRS are the most common type. Fusion partners for the CIC gene include DUX4, FOXO4, and the recently recognizedNUTM1. Rare cases of CIC::NUTM1 sarcoma in pediatric patients have recently been reported in brain, kidney, bone, and soft tissues. However, such cases have not been identified in the soft tissues of the limbs. CASE PRESENTATION: We reported a case of CIC::NUTM1 sarcoma located in the right upper limb of an 18-year-old man. The tumor displayed morphologic features typical of CIC::DUX4 sarcomas, with small- to medium-sized round cells, a lobular pattern, focal spindling, myxoid stroma, and patchy necrosis. The tumor diffusely expressed NUTM1, was positive for WT1cter at weak to moderate intensity, and was focally positive for CD99, while it was negative for keratins, EMA, P40, MyoD1, myogenin, NKX2.2, BCOR, and pan-TRK. Fluorescence in situ hybridization analyses revealed cleavage of the CIC and NUTM1 genes. CONCLUSION: CIC::NUTM1 sarcomas represent a novel molecular variant of CRS with a preference for the central nervous system and younger pediatric persons. Its morphology and phenotype may be mistaken for NUT carcinomas, and the behavior is more progressive than other forms of CRS. For this rare and newly discovered gene fusion variant, it is necessary to integrate molecular and immunohistochemical findings with morphologic features in the diagnosis of undifferentiated neoplasms.

AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma.

The comprehensive analysis of single or multiple microarray datasets is currently available in Gene Expression Omnibus (GEO) databases, with several studies having identified genes strongly associated with the development of lung adenocarcinoma (LUAD). However, the mechanisms of LUAD development remain largely unknown and has not yet been systematically studied; thus, further studies are required in this field. In the present study, weighted gene co-expression network analysis (WGCNA) was used for the evaluation of key genes with potential high risk of LUAD, and to provide more reliable evidence concerning its pathogenesis. The GSE140797 dataset from the high-throughput GEO database was downloaded and was first analyzed using the Limma package in the R language in order to determine the differentially expressed genes. The dataset was then analyzed using the WGCNA package to analyze the co-expressed genes, and the modular genes with the highest correlation with the clinical phenotype were identified. Subsequently, the pathogenic genes shared in common between the result of the two analyses were imported into the STRING database for protein-protein interaction network analysis. The hub genes were screened out using Cytoscape, and then The Cancer Genome Atlas analysis, receiver operating characteristic analysis and survival analysis were subsequently performed. Finally, the key genes were evaluated using reverse transcription-quantitative PCR and western blot analysis. Bioinformatics analysis of the GSE140797 dataset revealed eight key genes: AURKA, BUB1, CCNB1, CDK1, MELK, NUSAP1, TOP2A and PBK. Finally, the AURKA, TOP2A and MELK genes were evaluated in samples from patients with lung cancer using WGCNA and RT-qPCR, western blot analysis experiments, providing basis for further research on the mechanisms of LUAD development and targeted therapy.

Placental pathology of the third trimester pregnant women from COVID-19.

AIMS: To explore the clinical characteristics and placental pathological changes of pregnant women with 2019 novel coronavirus (CoV) disease (COVID-19) in the third trimester, and to assess the possibility of vertical transmission. METHODS AND RESULTS: The placenta tissues were evaluated by using immunohistochemistry for inflammatory cells and Hofbauer cells, and using severe acute respiratory syndrome (SARS) CoV-2 RNA Fluorescence In-Situ Hybridization (FISH) and SARS-CoV-2 spike protein immunofluorescence (IF) double staining. All eight placentas from the third trimester pregnancy women were studied. All patients were cured, no clinical or serological evidence pointed to vertical transmission of SARS-CoV-2. Features of maternal vascular malperfusion (MVM) such as increased syncytial knots were present in all 8 cases (8/8), and increased focal perivillous fibrin depositions were presented in 7 cases (7/8). No significate chronic histiocytic intervillositis was noted in the placenta. The number of macrophages and inflammatory cells such as T cells, B cells and plasma cells in the placental villous was not significantly increased in all cases. Moreover, all of eight cases demonstrated negative results by FISH using a SARS-CoV-2 virus RNA probe and by IF using a monoclonal antibody against SARS-CoV-2 spike protein. CONCLUSIONS: We found no evidence of vertical transmission and adverse maternal-fetal outcomes in the placentas of third trimester COVID-19 pregnancy women, which provided further information for the clinical management of those women in the third trimester. However, further studies are still needed for patients with infections in different stage of gestation, especially in first and second trimester.

MFAP2 is overexpressed in gastric cancer and promotes motility via the MFAP2/integrin α5ß1/FAK/ERK pathway.

Gastric cancer (GC) is one of the most common malignancies and its prognosis is extremely poor. This study identifies a novel oncogene, microfibrillar-associated protein 2 (MFAP2) in GC. With integrative reanalysis of transcriptomic data, we found MFAP2 as a GC prognosis-related gene. And the aberrant expression of MFAP2 was explored in GC samples. Subsequent experiments indicated that silencing and exogenous MFAP2 could affect motility of cancer cells. The inhibition of silencing MFAP2 could be rescued by another FAK activator, fibronectin. This process is probably through affecting the activation of focal adhesion process via modulating ITGB1 and ITGA5. MFAP2 regulated integrin expression through ERK1/2 activation. Silencing MFAP2 by shRNA inhibited tumorigenicity and metastasis in nude mice. We also revealed that MFAP2 is a novel target of microRNA-29, and miR-29/MFAP2/integrin α5ß1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression. In conclusion, our data identified MFAP2 as a novel oncogene in GC and revealed that miR-29/MFAP2/integrin α5ß1/FAK/ERK1/2 could be an important oncogenic pathway in GC progression.

Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate ischemic neuronal death by targeting miR-21/PDCD4 signaling pathway.

Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been demonstrated as an important regulator in diverse human cancers. However, its function and regulatory mechanism in ischemic stroke remains largely unknown. Here, we report that MEG3 is physically associated with microRNA-21 (miR-21), while miR-21 is downregulated following ischemia in the ischemic core in vitro and in vivo, which is opposite to MEG3. Besides, overexpression of miR-21 protects oxygen-glucose deprivation and reoxygenation (OGD/R)-induced apoptotic cell death. Furthermore, MEG3 functions as a competing endogenous RNAs (ceRNAs) and competes with programmed cell death 4 (PDCD4) mRNA for directly binding to miR-21, which mediates ischemic neuronal death. Knockdown of MEG3 protects against ischemic damage and improves overall neurological functions in vivo. Thus, our data uncovers a novel mechanism of lncRNA MEG3 as a ceRNA by targeting miR-21/PDCD4 signaling pathway in regulating ischemic neuronal death, which may help develop new strategies for the therapeutic interventions in cerebral ischemic stroke.