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Long noncoding RNA PTENP1 affects the recovery of spinal cord injury by regulating the expression of miR‐19b and miR‐21
Author(s) -
Wang Zhan,
Song Yuxin,
Han Xingwen,
Qu Peng,
Wang Wenji
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29253
Subject(s) - tensin , small hairpin rna , pten , biology , downregulation and upregulation , microbiology and biotechnology , cancer research , apoptosis , gene knockdown , pi3k/akt/mtor pathway , signal transduction , biochemistry , gene
Exosomes derived from differentiated P12 cells and MSCs were proved to suppress apoptosis of neuron cells, and phosphatase and tensin homolog pseudogene 1 (PTENP1) was reported to inhibit cell proliferation. In this study, we aimed to investigate the role of PTENP1 in the process of post‐spinal cord injury (SCI) recovery, so as to evaluate the therapeutic effects of exosomes derived from MSCs transfected with PTENP1 short hairpin RNA (shRNA), as a type of novel biomarkers in the treatment of SCI. Electron microscopy was used to observe the morphology of different exosomes. Real‐time polymerase chain reaction and western blot, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays, flow cytometry, Nissl staining, immunohistochemistry assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were conducted to investigate and validate the underlying molecular signaling pathway. PTENP1‐shRNA downregulated PTENP1 and PTEN while upregulating miR‐21 and miR‐19b. PTENP1‐shRNA also accelerated cell apoptosis and reduced cell viability. In addition, PTENP1 reduced the miR‐21 and miR‐19b expression by directly targeting miR‐21 and miR‐19b. Meanwhile, both miR‐21 and miR‐19b reduced the expression of PTEN by directly targeting the 3′‐untranslated region of PTEN. Furthermore, PTEN level and apoptosis index of neuron cells was the highest in the SCI group, while the treatment with exosomes+PTENP1‐shRNA reduced the PTEN expression to a level similar to that in the sham group. Finally, PTENP1 inhibited miR‐21 and miR‐19b expression but upregulated PTEN expression. The upregulation of miR‐21/miR‐19b also suppressed the apoptosis of neuron cells by downregulating the PTEN expression. PTENP1 is involved in the recovery of SCI by regulating the expression of miR‐19b and miR‐21, and exosomes from PTENP1‐shRNA‐transfected cells may be used as a novel biomarker in SCI treatment.