LncRNA FOXC2-AS1 protects cardiomyocytes from doxorubicin-induced cardiotoxicity through activation of WNT1-inducible signaling pathway protein-1

Doxorubicin (Dox) is an anthracycline antibiotic that has been used to treat different cancers. Dox-induced cardiotoxicity is common in clinical practice, while its mechanism is unknown. It has been proved that lncRNA FOXC2-AS1 may promote doxorubicin resistance and WNT1-inducible signaling pathway protein-1 (WISP1) blocks doxorubicin-induced cardiomyocyte death. Our study aimed to investigate the involvement of lncRNA FOXC2-AS1 and WISP1 in doxorubicin-induced cardiotoxicity and to explore their interactions. In our study we observed that FOXC2-AS1 and WISP1 mRNA were downregulated in heart tissues of mice with Dox-induced cardiotoxicity. FOXC2-AS1 and WISP1 mRNA expression were positively correlated in mice with Dox-induced cardiotoxicity but not in healthy mice. Overexpression of FOXC2-AS1 promoted to viability of mice cardiomyocytes under Dox treatment and also increased the expression level of WISP1. In contrast, WISP1 overexpression showed no significant effect on FOXC2-AS1. We therefore conclude that lncRNA FOXC2-AS1 may upregulate WISP1 to protect cardiomyocytes from doxorubicin-induced cardiotoxicity.     

Genome-wide identification and characterization of novel microRNAs in seed development of soybean

MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression in eukaryotes. However, the information about miRNAs population and their regulatory functions involving in soybean seed development remains incomplete. Base on the Dicer-like1-mediated cleavage signals during miRNA processing could be employed for novel miRNA discovery, a genome-wide search for miRNA candidates involved in seed development was carried out. As a result, 17 novel miRNAs, 14 isoforms of miRNA (isomiRs) and 31 previously validated miRNAs were discovered. These novel miRNAs and isomiRs represented tissue-specific expression and the isomiRs showed significantly higher abundance than that of their miRNA counterparts in different tissues. After target prediction and degradome sequencing data-based validation, 13 novel miRNA–target pairs were further identified. Besides, five targets of 22-nt iso-gma-miR393h were found to be triggered to produce secondary trans-acting siRNA (ta-siRNAs). Summarily, our results could expand the repertoire of miRNAs with potentially important functions in soybean.     

Medium chain carboxylic acids production from waste biomass: Current advances and perspectives

Alternative chemicals to diverse fossil-fuel-based products is urgently needed to mitigate the adverse impacts of fossil fuel depletion on human development. To this end, researchers have focused on the production of biochemical from readily available and affordable waste biomass. This is consistent with current guidelines for sustainable development and provides great advantages related to economy and environment. The search for suitable biochemical products is in progress worldwide. Therefore, this review recommends a biochemical (i.e., medium chain carboxylic acids (MCCAs)) utilizing an emerging biotechnological production platform called the chain elongation (CE) process. This work covers comprehensive introduction of the CE mechanism, functional microbes, available feedstock types and corresponding utilization strategies, major methods to enhance the performance of MCCAs production, and the challenges that need to be addressed for practical application. This work is expected to provide a thorough understanding of the CE technology, to guide and inspire researchers to solve existing problems in depth, and motivate large-scale MCCAs production.     

Metformin promotes survivin degradation through AMPK/PKA/GSK-3β-axis in non–small cell lung cancer

Metformin, a first-line antidiabetic drug, has been reported with anticancer activities in many types of cancer. However, its molecular mechanisms remain largely unknown. As a member of inhibitor of apoptosis proteins, survivin plays an important role in the regulation of cell death. In the present study, we investigated the role of survivin in metformin-induced anticancer activity in non–small cell lung cancer in vitro. Metformin mainly induced apoptotic cell death in A549 and H460 cell lines. It remarkably suppressed the expression of survivin, decreased the stability of this protein, then promoted its proteasomal degradation. Moreover, metformin greatly suppressed protein kinase A (PKA) activity and induced its downstream glycogen synthase kinase 3β (GSK-3β) activation. PKA activators, both 8-Br-cAMP and forskolin, significantly increased the expression of survivin. Consistently both GSK-3β inhibitor LiCl and siRNA restored the expression of survivin in lung cancer cells. Furthermore, metformin induced adenosine 5′-monophosphate-activated protein kinase (AMPK) activation. Suppression of the activity of AMPK with Compound C reversed the degradation of survivin induced by metformin, and meanwhile, restored the activity of PKA and GSK-3β. These results suggest that metformin kills lung cancer cells through AMPK/PKA/GSK-3β-axis–mediated survivin degradation, providing novel insights into the anticancer effects of metformin.     

Overexpression of heme oxygenase-1 in microenvironment mediates vincristine resistance of B-cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Chemoresistance often causes treatment failure of B-cell acute lymphoblastic leukemia (B-ALL). However, the mechanism remains unclear at present. Herein, overexpression of heme oxygenase-1 (HO-1) was found in the bone marrow stromal cells (BMSCs) from B-ALL patients developing resistance to vincristine (VCR), a chemotherapeutic agent. Two B-ALL cell lines Super B15 and CCRF-SB were cocultured with BMSCs transfected with lentivirus to regulate the expression of HO-1. Silencing HO-1 expression in BMSCs increased the apoptotic rates of B-ALL cell lines induced by VCR, whereas upregulating HO-1 expression reduced the rate. Cell cycle can be arrested in the G2/M phase by VCR. In contrast, B-ALL cells were arrested in the G0/G1 phase due to HO-1 overexpression in BMSCs, which avoided damage from the G2/M phase. Vascular endothelial growth factor (VEGF) in BMSCs, as a key factor in the microenvironment-associated chemoresistance, was also positively coexpressed with HO-1. VEGF secretion was markedly increased in BMSCs with HO-1 upregulation but decreased in BMSCs with HO-1 silencing. B-ALL cell lines became resistant to VCR when cultured with VEGF recombinant protein, so VEGF secretion induced by HO-1 expression may promote the VCR resistance of B-ALL cells. As to the molecular mechanism, the PI3K/AKT pathway mediated regulation of VEGF by HO-1. In conclusion, this study clarifies a mechanism by which B-ALL is induced to resist VCR through HO-1 overexpression in BMSCs, and provides a novel strategy for overcoming VCR resistance in clinical practice.