scholarly journals MicroRNA-222 Transferred From Semen Extracellular Vesicles Inhibits Sperm Apoptosis by Targeting BCL2L11

Author(s):  
Yaqun Ding ◽  
Ning Ding ◽  
Yu Zhang ◽  
Shenmin Xie ◽  
Mengna Huang ◽  
...  

Seminal plasma contains a large number of extracellular vesicles (EVs). However, the roles of these EVs and their interactions with sperm are not clear. To identify the important molecules affecting sperm motility in EVs, we analyzed RNA from seminal plasma EVs of boars with different sperm motility using whole-transcriptome sequencing and proteomic analysis. In total, 7 miRNAs, 67 lncRNAs, 126 mRNAs and 76 proteins were differentially expressed between the two groups. We observed that EV-miR-222 can obviously improve sperm motility. In addition, the results suggested that miR-222 was transferred into sperm by the EVs and that miR-222 affected sperm apoptosis by inhibiting the expression of EGFR, BCL2L11, BAX, CYCs, CASP9 and CASP3. The results of electron microscopy also showed that overexpression of miR-222 in EVs could reduce sperm apoptosis. The study of the whole transcriptomes and proteomes of EVs in boar semen revealed some miRNAs may play an important role in these EVs interactions with Duroc sperm, and the findings suggest that the release of miR-222 by semen EVs is an important mechanism by which sperm viability is maintained and sperm apoptosis is reduced. Our studies provide a new insight of miR-222 in EVs regulation for sperm motility and sperm apoptosis.

2021 ◽  
pp. 106689692110313
Author(s):  
Alexander M. Strait ◽  
Julia A. Bridge ◽  
Anthony J. Iafrate ◽  
Marilyn M. Li ◽  
Feng Xu ◽  
...  

Myofibroblastoma is a rare, benign stromal tumor with a diverse morphologic spectrum. Mammary-type myofibroblastoma (MTMF) is the extra-mammary counterpart of this neoplasm and its occurrence throughout the body has become increasingly recognized. Similar morphologic variations of MTMF have now been described which mirror those seen in the breast. We describe a case of intra-abdominal MTMF composed of short fascicles of eosinophilic spindle cells admixed with mature adipose tissue. The spindle cells stained diffusely positive for CD34, desmin, smooth muscle actin, and h-caldesmon by immunohistochemistry. Concurrent loss of RB1 (13q14) and 13q34 loci were confirmed by fluorescence in situ hybridization whereas anchored multiplex PCR and whole transcriptome sequencing did not reveal any pathognomonic fusions suggesting an alternative diagnosis. To the best of our knowledge this is the first documented case of leiomyomatous variant of MTMF.


Author(s):  
Ana Carolina Pedrosa ◽  
Mariana A. Torres ◽  
Diego V. Alkmin ◽  
Jorge E.P. Pinzon ◽  
Simone Maria M.K. Martins ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4035-4035
Author(s):  
Deqiang Wang ◽  
Xiaofeng Chen ◽  
Yaping Xu ◽  
Yuange He ◽  
Lifeng Li ◽  
...  

4035 Background: Gastric adenocarcinoma (GAC) is with a complex microenvironment of tumor cells. A better understanding of the immune landscape of GACs may lead to the improved treatment strategies with ICIs. Methods: To determine whether the molecular characteristics can serve in prognostic stratification of GACs, tumor tissue and blood samples were collected from 231 GAC patients. The median follow-up time was 34 months. The TCR profile was determined by TCR-β CDR3 sequencing while mutation and gene expression profiles were determined by whole exon and whole transcriptome sequencing, respectively. Tumour-infiltrating immune cells were characterized using immunofluorescence (IF) staining. Results: The results showed the OS of patients with high levels of TCR clonality (TCR clonal expansion) was significantly improved compared with patients with low levels (HR = 1.80 and 2.22, p = 0.022 and 0.008, respectively) in the whole group and in the subgroup of patients with stages IB to III disease. Furthermore, low local clonality was an independent risk factor for OS (adjusted-HR = 1.68 and 1.95, p = 0.049 and 0.029, respectively). Thus, TCR clonal expansion in tumour tissue had a strong prognostic value for GAC patients, independent of clinicopathological factors. Based on whole exon and whole transcriptome sequencing, RNF43/FBXW7/ARID2 mutations and local TCR clonality jointly impacted prognosis (p < 0.001), and functional changes in corresponding Wnt pathway/Notch pathway/SWI/SNF complex characterized a GAC subset with enhanced tumour immunogenicity and TCR clonal expansion. TCR CDR3 sequence similarity comparisons yielded clusters of TCR clones of likely similar functions. The most expansive TCR clusters negatively correlated with the percentage of subclonal mutations (Pearson r = -0.8183, p < 0.001), indicating that tumors with less genomic heterogeneity might induce a greater immune response. By IF staining and mutual correlation analysis, only M1 macrophages showed a significant positive correlation with local TCR clonality for epithelia, stroma, and total cell counts. Tumors were categorized according to the density of M1 macrophages, M1 macrophage infiltrated subtype was associated with favorable OS (p = 0.040 and 0.043) and its combination with the local TCR clonality improved prognosis stratification (p < 0.001). Finally, the scoring by local TCR clonality, RNF43/FBXW7/ARID2 mutations and M1 infiltration determined the best prognosis (p < 0.001). Conclusions: TCR profiles were associated with genomic alterations and may serve as a prognostic biomarker for GACs. A multi-omic model including TCR profiles might produce an improved stratification for treatments and outcomes.


2020 ◽  
Author(s):  
Fei Yao ◽  
Chuanren Zhou ◽  
Qiyou Huang ◽  
Xiaoying Huang ◽  
Jie Chen ◽  
...  

Abstract Background: Chemo-resistance is a major clinical obstacle to the treatment of colorectal cancer (CRC), mRNAs and non-coding RNAs (ncRNAs) have been reported to modulate the development of chemo-resistance. However, the profiles of mRNAs and ncRNAs as well as competing endogenous RNA (ceRNA) networks in CRC chemo-resistance are still unclear, and whether different drug resistance of CRC have the same mechanisms also needs to be explored. This study aims to uncover the expression of mRNAs and ncRNAs in parental cell lines and different chemo-resistant cell lines, and construct ceRNA regulatory networks by whole-transcriptome sequencing.Methods: The expression of mRNAs and ncRNAs in parental cell lines and drug-resistant cell lines were identified by whole-transcriptome sequencing and bioinformatics methods.Results: A total of 1779 mRNAs, 64 miRNAs, 11 circRNAs and 295 lncRNAs were common differentially expressed in two different chemo-resistant cell lines when compared with the control. In addition, 5,767 lncRNA-miRNA-mRNA relationship pairs and 47 circRNA-miRNA-mRNA pathways were constructed according to ceRNA regulatory rules, in which AC109322.2-hsa-miR-371a-5p-BTNL3 and hsacirc_027876-hsa-miR-582-3p-FREM1 were identified as the most potential ceRNA networks involved in drug resistance to CRC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of two ceRNA regulatory networks showed that the TNF signaling pathway may be crucial in the process of CRC drug resistance.Conclusions: A large number of mRNAs and ncRNAs in chemo-resistant cell lines were different expressed, which may play pivotal roles in development of drug resistance through the ceRNA regulatory network. This study may improve our understanding of the underlying mechanisms and provide a promising therapeutic strategy for CRC chemo-resistance.


2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Ka-Kyung Kim ◽  
Byung-Joon Seung ◽  
Dohyun Kim ◽  
Hee-Myung Park ◽  
Sejoon Lee ◽  
...  

2011 ◽  
Author(s):  
Takashi Kohno ◽  
Hitoshi Ichikawa ◽  
Yasushi Totoki ◽  
Kazuki Yasuda ◽  
Masaki Hiramoto ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document