MicroRNA-199a/b-3p is downregulated in several types of aggressive cancer, and its decrement significantly correlates with poor survival. Here, we aim to investigate the biological function of miR-199a/b-3p and its regulation of target genes in breast cancer cells with highly metastatic potential. In addition, we found that miR-199a/b-3p expression was much lower in MDA-MB-231, CAL120, and HCC1395 breast cancer cells with highly metastatic potential. Functional assays showed that restored miR-199a/b-3p expression inhibited MDA-MB-231 cell growth, cell-cycle progression, migration, and invasion. In addition, we experimentally demonstrated that PAK4 was the direct target of miR-199a/b-3p, hypo-expression of PAK4 suppressed proliferation, migration and invasion of MDA-MB-231 cells, and overexpression of PAK4 significantly rescued the inhibitory effect of miR-199a/b-3p on MDA-MB-231 cell growth, migration, and invasion. Further, we also observed that miR199a/b-3p could inactivate the PAK4/MEK/ERK signaling pathway. Thus, miR-199a/b-3p functions as a tumor suppressor and has an important role in breast cancer metastasis through PAK4/MEK/ERK signaling pathway. V C 2015 IUBMB Life, 67(10): [768][769][770][771][772][773][774][775][776][777] 2015

Axion is a popular candidate for dark matter particles. Axionic dark matter may form Bose-Einstein condensate and may be gravitationally bound to form axion clumps. Under the presence of electromagnetic waves with frequency ω= ma/ 2, where ma is the axion mass, a resonant enhancement may occur, causing an instability of the axion clumps. With analytical and numerical approaches, we study the resonant instability of axionic dark matter clumps with infinite homogeneous mass distribution, as well as distribution with a finite boundary. After taking realistic astrophysical environments into consideration, including gravitational redshift and plasma effects, we obtain an instability region in the axion density—clump size parameter space with given mass and coupling of axions. In particular, we show that, for axion clumps formed by the QCD axions in equilibrium, no resonant instability will occur.

The increasing prevalence of antibacterial resistance globally underscores the urgent need for updated antimicrobial peptides (AMPs). Here, we describe a strategy for inducing the self-assembly of protegrin-1 (PG-1) into nanostructured antimicrobial agents with significantly improved pharmacological properties. Our strategy involves PEGylation in the terminals of PG-1 and subsequent self-assembly in aqueous media in the absence of exogenous excipients. Compared with the parent PG-1, the therapeutic index (TI) of NPG 750 (TI Gram-negative bacteria = 17.07) and CPG 2000 (TI All = 26.02) was increased. Importantly, NPG 750 and CPG 2000 offered higher stability toward trypsin degradation. Mechanistically, NPG 750 and CPG 2000 exerted their bactericidal activity by membrane-active mechanisms due to which microbes were not prone to develop resistance. Our findings proved PEGylation as a simple yet versatile strategy for generating AMP-derived bioactive drugs with excellent antitrypsin hydrolytic ability and lower cytotoxicity. This provides a theoretical basis for the further clinical application of AMPs.

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