Breast cancer is one of the most frightful causes of death among females worldwide. Accumulating evidence attached the importance of microRNAs negative regulation to tumorigenesis in breast cancer, suggesting novel cancer therapies targeting microRNAs modulation. Recent studies demonstrated that isoliquiritigenin could inhibit breast cancer cells proliferation and migration, but the underlying mechanism is still limited. In this study, the anti-cancer effects as well as the detailed mechanisms of isoliquiritigenin were explored. The results proved that isoliquiritigenin could negatively regulate breast cancer growth through the induction of apoptosis. We also verified the anti-cancer effect of isoliquiritigenin on migration and invasion, and identified highly expressed miR-374a as one of the main microRNAs down-regulated by isoliquiritigenin treatment in breast cancer. Further study displayed that isoliquiritigenin increased PTEN expression through the decrease of miR-374a expression to inhibit the aberrant Akt signaling. Our findings suggest isoliquiritigenin as a novel anti-cancer candidate significantly regulating miR-374a/PTEN/Akt axis in microRNA-based breast cancer therapies.
A PAL gene designated as JcPAL1 was cloned from J. curcas L. The full-length is 2336 bp in size with one intron and two exons, encoding a polypeptide of 713 amino acids. Its 5'-upstream region is rich in putative cis-elements including not only PAL typical TATA box, L-box and transcriptional initiation site (TIS) but also light responding motifs. Expression pattern analysis indicated that JcPAL1 were expressed in all tissues, most highly in flowers. When Treated with ABA, GA3, high and low temperature, expression of JcPAL1 were induced. Recombinant JcPAL1 has a pH optimum at 8.7 and a temperature optimum at 60°C in 100 mM Tris-HCl buffer. The Km and Kcat values are 0.125 mM and 1.73 S(-1) for L: -phenylalanine, and 1.312 mM and 0.109 S(-1) for L: -tyrosine, respectively. These findings suggested that JcPAL1 might involve in the J. curcas responding to various stresses and L: -Phe should be its true physiological substrate. This study is essential prior to uncover whether and how the PAL initiated phenylpropanoid metabolic networks functioning in the defense responses of J. curcas.
Summary
Magnolia officinalis
, a representative tall aromatic tree of the Magnoliaceae family, is a medicinal plant that is widely used in diverse industries from medicine to cosmetics. We report a chromosome-scale draft genome of
M. officinalis
, in which ∼99.66% of the sequences were anchored onto 19 chromosomes with the scaffold N50 of 76.62 Mb. We found that a high proportion of repetitive sequences was a common feature of three Magnoliaceae with known genomic data. Magnoliids were a sister clade to eudicots-monocots, which provided more support for understanding the phylogenetic position among angiosperms. An ancient duplication event occurred in the genome of
M. officinalis
and was shared with Lauraceae. Based on RNA-seq analysis, we identified several key enzyme-coding gene families associated with the biosynthesis of lignans in the genome. The construction of the
M. officinalis
genome sequence will serve as a reference for further studies of
Magnolia,
as well as other Magnoliaceae.
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