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HnRNPL promotes Wilms tumor progression by regulating the p53 and Bcl2 pathways
- Source :
- OncoTargets and Therapy. 12:4269-4279
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
Abstract
- Background: Wilms tumor (WT) is the most common renal tumor in children with diffusely anaplastic or unfavorable histology, indicative of a poor prognosis. Heterogeneous nuclear ribonucleoprotein L (hnRNPL) is an RNA-binding protein (RBP) and a regulator of alternative RNA splicing that plays an important role in the occurrence and development of several cancers. Methods: Next generation sequencing technologies was used to discovery differentially expressed genes between WT and adjacent nontumors. The gene ontology (GO) analysis was performed to uncover the biological functions of differentially expressed genes, and the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was applied to find out the related signal pathways. Expression levelsof hnRNPL with WT tissues and cells were determined by RT-qPCR.After silencing hnRNPL, the expression of hnRNPL, p53 and Bcl-2 were detected by RT-qPCR and Western blot in WT cell line. The regulatory effects of hnRNPLon proliferative and apoptotic potentials of WT cells were evaluated by MTT and flow cytometry, respectively. RNA-binding protein immuno-precipitation was used to confirm the direct interaction of hnRNPL with p53 mRNA. Mouse xenograft models ofhnRNPL knockdown were established to test the functions in the growth of WT in vivo. Results: High levels of hnRNPL were expressed in WT tissues and cells. Functional analysis revealed that hnRNPL silencing suppressed cell proliferation and promoted cell apoptosis in WT. Molecular mechanism exploration indicated that hnRNPL directly targeted p53. Moreover, knockdown of hnRNPL inhibited the expression of p53 and Bcl2 in WT. Additionally, hnRNPL silencing inhibited the growth of xenograft tumors in vivo. Conclusion: HnRNPL act as p53 mRNA-binding protein, which plays an important role in the proliferation and apoptosis of WT through p53 and Bcl2 pathways and these findings provide new insights into the mechanism of WT pathogenesis.
- Subjects :
- 0301 basic medicine
Messenger RNA
Gene knockdown
medicine.diagnostic_test
Cell growth
Alternative splicing
Biology
Flow cytometry
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Oncology
Cell culture
030220 oncology & carcinogenesis
medicine
Gene silencing
Pharmacology (medical)
KEGG
Subjects
Details
- ISSN :
- 11786930
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- OncoTargets and Therapy
- Accession number :
- edsair.doi...........ec37508433bfd1df4c2e1b87b54b6206