Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Apr 2019
miR-100-5p confers resistance to ALK tyrosine kinase inhibitors Crizotinib and Lorlatinib in EML4-ALK positive NSCLC.
Lung cancer causes the highest number of cancer-related deaths worldwide. Resistance to therapy is a major clinical issue contributing to the poor prognosis of lung cancer. In recent years, targeted therapy has become a concept where subgroups of non-small cell lung cancer (NSCLC) with genetically altered receptor tyrosine kinases are targeted by tyrosine kinase inhibitors (TKIs). ⋯ We subjected our ALK TKI-refractory cancer cells along with parental cancer cells to systematic miRNA expression arrays. Furthermore, ALK TKI-refractory cancer cells were exposed to a synthetic miRNA inhibitory Locked Nucleic Acid (LNA)-library in the presence of ALK TKIs Crizotinib or Lorlatinib. The outcome of the combined approaches uncovered miR-100-5p to confer resistance to Crizotinib and Lorlatinib in EML4-ALK NSCLC cells and to be a potential therapeutic target in drug resistance.
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Biochem. Biophys. Res. Commun. · Mar 2019
Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE-/- mice via miR-let7 mediated infiltration and polarization of M2 macrophage.
Atherosclerosis is a chronic inflammatory disease of the vasculature. Exosomes derived from mesenchymal stem cells (MSCs) exert immunomodulatory and immunosuppressive effects; however, the MSCs-exosomes administration on atherosclerosis was unknown. Here, our ApoE-/- mice were fed a high-fat diet and received intravenous injections of exosomes from MSCs for 12 weeks. ⋯ In addition, MSCs-exosomes suppressed macrophage infiltration via miR-let7/IGF2BP1/PTEN pathway in the plaque. This finding extends our knowledge on MSCs-exosomes affect inflammation in atherosclerosis plaque and provides a potential method to prevent the atherosclerosis. Exosomes from MSCs hold promise as therapeutic agents to reduce the residual risk of coronary artery diseases.
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Biochem. Biophys. Res. Commun. · Feb 2019
Impact of sperm DNA fragmentation on ICSI outcome and incidence of apoptosis of human pre-implantation embryos obtained from in vitro matured MII oocytes.
Sperm DNA integrity and oocyte quality significantly affect embryo development and survival. The current study evaluated embryo development and quality, as well as the expression level of apoptosis-related genes and microRNAs in embryo derived from in vitro matured MII oocytes according to sperm DNA fragmentation (SDF) level. ⋯ The IVM oocytes, probably, did not suffice to recover the high level of paternal genomic damage and inhibition of apoptosis pathway beginning.
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Biochem. Biophys. Res. Commun. · Feb 2019
A novel lncRNA LOC101927746 accelerates progression of colorectal cancer via inhibiting miR-584-3p and activating SSRP1.
An increasing number of reports have indicated that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of colorectal cancer (CRC). However, many lncRNAs remain unidentified in CRC, and their functions are yet to be elucidated. In this study, we investigated the function of lncRNA LOC101927746 in CRC progression. ⋯ The expression of miR-584-3p was inversely correlated with either LOC101927746 or SSRP1 in CRC tissues. The overexpression of SSRP1 or inhibition of miR-584-3p could reverse the effects of LOC101927746 knockdown in CRC cells. Taken together, our results suggest that the LOC101927746/miR-584-3p/SSRP1 axis modulates CRC progression.
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Biochem. Biophys. Res. Commun. · Feb 2019
The SIRT2 inhibitor AK-7 decreases cochlear cell apoptosis and attenuates noise-induced hearing loss.
Oxidative damage plays a critical role in cochlear cell apoptosis, which is central to the physiopathology of noise-induced hearing loss (NIHL). Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase that regulates cellular response to oxidative stress, however, its role in NIHL remains poorly understood. Here, we report that SIRT2 is upregulated in the cochlea after noise exposure. ⋯ Moreover, AK-7 treatment reduces apoptosis of mouse inner ear HEI-OC1 cells exposed to oxidative stress in vitro. Taken together, these results suggest that SIRT2 inhibition with AK-7 reduces cochlear cell apoptosis through attenuating oxidative stress-induced damage, which may underlie its protective role against NIHL. This study also implies that AK-7 may have potential therapeutic significance in the intervention of NIHL.