scholarly journals Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Alessia Parascandolo ◽  
Francesca Rappa ◽  
Francesco Cappello ◽  
Jaehyup Kim ◽  
David A. Cantu ◽  
...  
Author(s):  
Litao Han ◽  
Hejing Lai ◽  
Yichen Yang ◽  
Jiaqian Hu ◽  
Zhe Li ◽  
...  

Abstract Background tRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive. Methods Papillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed. Results Herein, we have identified a 33 nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent. Conclusions Our study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.


Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1055
Author(s):  
Hersh Chaitin ◽  
Michael L. Lu ◽  
Michael B. Wallace ◽  
Yunqing Kang

Many decellularized extracellular matrix-derived whole organs have been widely used in studies of tissue engineering and cancer models. However, decellularizing porcine esophagus to obtain decellularized esophageal matrix (DEM) for potential biomedical applications has not been widely investigated. In this study a modified decellularization protocol was employed to prepare a porcine esophageal DEM for the study of cancer cell growth. The cellular removal and retention of matrix components in the porcine DEM were fully characterized. The microstructure of the DEM was observed using scanning electronic microscopy. Human esophageal squamous cell carcinoma (ESCC) and human primary esophageal fibroblast cells (FBCs) were seeded in the DEM to observe their growth. Results show that the decellularization process did not cause significant loss of mechanical properties and that blood ducts and lymphatic vessels in the submucosa layer were also preserved. ESCC and FBCs grew on the DEM well and the matrix did not show any toxicity to cells. When FBS and ESCC were cocultured on the matrix, they secreted more periostin, a protein that supports cell adhesion on matrix. This study shows that the modified decellularization protocol can effectively remove the cell materials and maintain the microstructure of the porcine esophageal matrix, which has the potential application of studying cell growth and migration for esophageal cancer models.


Oncotarget ◽  
2017 ◽  
Vol 8 (66) ◽  
pp. 110552-110565 ◽  
Author(s):  
Honggang Sun ◽  
Liqin He ◽  
Lan Ma ◽  
Tao Lu ◽  
Jianguo Wei ◽  
...  

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