Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie
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Biomed. Pharmacother. · Mar 2018
MiR-21 promotes ECM degradation through inhibiting autophagy via the PTEN/akt/mTOR signaling pathway in human degenerated NP cells.
Intervertebral disc degeneration (IDD) is the most common cause leading to low back pain, a highly prevalent, costly and crippling condition worldwide. Overexpression of miR-21 has been shown to promote proliferation of nucleus pulposus (NP) cells. However, it remains unclear whether miR-21 can promote the degradation of type II collagen (Col II) and aggrecan, two main extracellular matrix components within the disc. ⋯ Through gain-of-function and loss-of-function studies in human NP cells, miR-21 was shown to inhibit autophagy and then upregulate the expression of matrix metalloproteinase (MMP)-3 and MMP-9, leading to increased degradation of Col II and aggrecan. Mechanistically, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-21, and activated PTEN/ Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in miR-21-induced autophagy inhibition and Col II and aggrecan breakdown. Taken together, these results suggest that miR-21 contributes to Col II and aggrecan catabolism by inhibiting autophagy via the PTEN/Akt/mTOR signaling pathway in human NP cells.
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Biomed. Pharmacother. · Feb 2018
Retinoid interferon-induced mortality19 (GRIM19) inhibits proliferation and invasion in rheumatoid arthritis fibroblast-like synoviocytes.
Rheumatoid arthritis (RA) fibroblast-like synoviocytes (RA-FLS) are reportedly involved in RA initiation, progression, and perpetuation. Previously a study showed that retinoid interferon-induced mortality 19 (GRIM19) improved the clinical and histological features of collagen-induced arthritis (CIA),and also inhibited osteoclast formation. However, the role of GRIM19 in RA-FLS remains unclear. ⋯ GRIM19significantly inhibited proliferation, migration, and invasion; promoted apoptosis; and suppressed inflammatory cytokine secretion by RA-FLS. Moreover, GRIM19 overexpression significantly decreasedthe expression levels of signal transducer and activator of transcription 3(STAT3)and its downstreamproteins,CyclinD1, Bcl-2, and MMP-9. These data indicate that promoting the expression of GRIM19 may yield therapeutic benefits in the treatment of RA.
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Biomed. Pharmacother. · Feb 2018
Long non-coding RNA HNF1A-AS1 promotes cell proliferation and invasion via regulating miR-17-5p in non-small cell lung cancer.
Long non-coding RNA HNF1A-antisense 1 (lncRNA HNF1A-AS1) plays important roles in the progression of human tumors. The aim of this study is to unravel the underlying mechanism of HNF1A-AS1 in non-small cell lung cancer (NSCLC). In the present study, we found that HNF1A-AS1 was upregulation in NSCLC tissues and cell lines. ⋯ Bioinformatics analysis and luciferase reporter assay revealed that HNF1A-AS1 interacted with miR-17-5p by directly targeting it. Rescue experiments showed that miR-17-5p suppression reversed the tumor-suppressing role of HNF1A-AS1 knockdown on NSCLC progression. Conclusion, our data indicated that lncRNA HNF1A-AS1 promoted lung cancer cells proliferation and invasion via regulating miR-17-5p, suggesting that HNF1A-AS1 could act as a potent therapeutic strategy for the treatment of NSCLC patients.
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Biomed. Pharmacother. · Feb 2018
CXCL16/ROCK1 signaling pathway exacerbates acute kidney injury induced by ischemia-reperfusion.
Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) resulting in an abrupt deterioration of kidney function. CXC chemokine ligand 16 (CXCL16) contributes significantly to the pathogenesis of renal injury. However, the signaling pathway mechanisms of CXCL16 in IRI-induced AKI remains obscured. ⋯ Administration of Y-27632 ameliorated apoptosis in the IRI-treated kidneys of mice. In injured HK-2 cells, CXCL16 activated ROCK1 resulting in the upregulation of caspase-3 protein and pro-inflammatory molecules, which was abolished by Y-27632. In summary, our findings demonstrate that CXCL16/ROCK1 signaling pathway may play an important role in the pathogenesis of IRI-induced AKI.
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Biomed. Pharmacother. · Feb 2018
Inhibition of p38 and ERK1/2 pathways by Sparstolonin B suppresses inflammation-induced melanoma metastasis.
Cancer related inflammation plays a fatal role in the metastatic process, which can foster tumor growth, angiogenesis and dissemination. Sparstolonin B (SsnB), derived from Chinese medicine of the tubers of Scirpus yagara, is a TLR2 and TLR4 antagonists. It has exhibited multiple activities of anti-inflammatory, anti-cancer, anti-obesity and anti-hepatitis. However, whether SsnB is involved in the regulation of inflammation-induced tumor metastasis is not well elucidated. ⋯ The present study reports a novel use of SsnB in mitigating TLRs ligands-induced melanoma metastasis by inhibition of p38 and ERK1/2 pathway.