5'-tRNA halves generated by IRE1α are linked to the ER stress response.

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5'-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNA to produce 5'-tRHs (5'-tRH-Gly) with highly selective target discrimination upon endoplasmic reticulum (ER) stress.

Making the Brightest Ones Dim: Maximizing the Photothermal Conversion Efficiency of BODIPY-Based Photothermal Agents.

The successful implementation of photothermal therapy (PTT) in cancer treatment hinges on the development of highly effective photothermal agents (PTAs). Boron dipyrromethene (BODIPY) dyes, being well known for their high brightness and quantum efficiencies, are the antithesis of PTAs. Nonetheless, a systematic exploration of the photophysics and photothermal characteristics of a series of π-extended BODIPY dyes with high absorptivity in the near-infrared (NIR) region has achieved superior photothermal conversion efficiencies (>90%), in both monomeric state and nanoparticles after encapsulation in a biocompatible polyethyleneglycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000].

Downregulation of DNA methylation enhances differentiation of THP-1 cells and induces M1 polarization of differentiated macrophages.

DNA methylation is an epigenetic modification that regulates gene expression and plays an essential role in hematopoiesis. UHRF1 and DNMT1 are both crucial for regulating genome-wide maintenance of DNA methylation. Specifically, it is well known that hypermethylation is crucial characteristic of acute myeloid leukemia (AML).

Activatable Fluorescent Probes Targeting Urokinase-Type Plasminogen Activator Receptor on the Cell Membrane.

Urokinase-type plasminogen activator receptor (uPAR) is a glycolipid-anchored protein located on the cell surface that is implicated in the promotion of metastasis. New fluorescent probes for the detection of uPAR expression that feature a rapid "turn-on" response are reported here. They consist of a donor-π-acceptor-based fluorophore conjugated with a uPAR-binding AE105 peptide.

Self-Assembled Peptidyl Aggregates for the Fluorogenic Recognition of Mitochondrial DNA G-Quadruplexes.

The selective monitoring of G-quadruplex (G4) structures in living cells is important to elucidate their functions and reveal their value as diagnostic or therapeutic targets. Here we report a fluorogenic probe (CV2) able to selectively light-up parallel G4 DNA over antiparallel topologies. CV2 was constructed by conjugating the excimer-forming CV dye with a peptide sequence (l-Arg-l-Gly-glutaric acid) that specifically recognizes G4s.

FOXL2 and FOXA1 cooperatively assemble on the TP53 promoter in alternative dimer configurations.

Although both the p53 and forkhead box (FOX) family proteins are key transcription factors associated with cancer progression, their direct relationship is unknown. Here, we found that FOX family proteins bind to the non-canonical homotypic cluster of the p53 promoter region (TP53). Analysis of crystal structures of FOX proteins (FOXL2 and FOXA1) bound to the p53 homotypic cluster indicated that they interact with a 2:1 stoichiometry accommodated by FOX-induced DNA allostery.

Development of DNA aptamers specific for small therapeutic peptides using a modified SELEX method.

Aptamers are short single-stranded DNA or RNA oligonucleotides capable of binding with high affinity and specificity to target molecules. Because of their durability and ease of synthesis, aptamers are used in a wide range of biomedical fields, including the diagnosis of diseases and targeted delivery of therapeutic agents. The aptamers were selected using a process called systematic evolution of ligands by exponential enrichment (SELEX), which has been improved for various research purposes since its development in 1990.

Anticancer activity and metabolic profile alterations by ortho-topolin riboside in in vitro and in vivo models of non-small cell lung cancer.

Lung cancer has the highest incidence and mortality rates among all types of cancer worldwide, and 80%-85% of patients with lung cancer are diagnosed with non-small cell lung cancer (NSCLC), which has 5-year survival rate of only 5% at advanced stages. Development of new therapeutic agents and strategies is required to enhance the treatment efficiency in patients with NSCLC. Metabolic alterations and anticancer effects of plant hormones and their derivatives have not been investigated in NSCLC in vitro and in vivo.

Gold nanoparticle-DNA aptamer-assisted delivery of antimicrobial peptide effectively inhibits Acinetobacter baumannii infection in mice.

Acinetobacter baumannii causes multidrug resistance, leading to fatal infections in humans. In this study, we showed that Lys AB2 P3-His-a hexahistidine-tagged form of an antimicrobial peptide (AMP) loaded onto DNA aptamer-functionalized gold nanoparticles (AuNP-Apt)-can effectively inhibit A. baumannii infection in mice.

A low dose of bisphenol A stimulates estradiol production by regulating β-catenin-FOXL2-CYP19A1 pathway in human ovarian granulosa cells.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical that interferes with normal steroid hormone production in various species. However, the underlying mechanism of the effect of BPA on steroid production in the human ovary is not well understood. In the present study, we found that BPA, at very low concentrations (10 to 10 M), significantly increased the expression of FOXL2, a transcriptional factor essential for proper ovarian development and function, in a human ovarian granulosa cell-derived cell line (KGN).

Integrative Metabolomic and Lipidomic Profiling of Lung Squamous Cell Carcinoma for Characterization of Metabolites and Intact Lipid Species Related to the Metastatic Potential.

SQCC is a major type of NSCLC, which is a major cause of cancer-related deaths, and there were no reports regarding the prediction of metastatic potential of lung SQCC by metabolomic and lipidomic profiling. In this study, metabolomic and lipidomic profiling of lung SQCC were performed to predict its metastatic potential and to suggest potential therapeutic targets for the inhibition of lung SQCC metastasis. Human bronchial epithelial cells and four lung SQCC cell lines with different metastatic potentials were analyzed using gas chromatography-mass spectrometry and direct infusion-mass spectrometry.

Guanylate-binding proteins induce apoptosis of leukemia cells by regulating MCL-1 and BAK.

Interferon-inducible guanylate-binding proteins (GBPs) are well-known for mediating host-defense mechanisms against cellular pathogens. Emerging evidence suggests that GBPs are also implicated in tumorigenesis; however, their underlying molecular mechanism is still unknown. In this study, we identified that GBP1 and GBP2 interact with MCL-1, the key prosurvival member of the BCL-2 family, via its BH3 domain.

Native Chemical Ligation-Based Fluorescent Probes for Cysteine and Aminopeptidase N Using meso-thioester-BODIPY.

meso-Carboxyl-BODIPY responds to small electronic changes resulting from acyl substitution reactions with a marked change in fluorescence. Herein, the minute changes that accompany the thioester to amide conversion encountered in native chemical ligation (NCL) are exploited in the construction of fluorescent "turn-on" probes. Two fluorogenic probes, 1 a and 4, derived from a meso-thioester-BODIPY scaffold, were designed for the selective detection of cysteine (1 a) and aminopeptidase N (4), respectively.

Endoribonuclease-mediated control of hns mRNA stability constitutes a key regulatory pathway for Salmonella Typhimurium pathogenicity island 1 expression.

Bacteria utilize endoribonuclease-mediated RNA processing and decay to rapidly adapt to environmental changes. Here, we report that the modulation of hns mRNA stability by the endoribonuclease RNase G plays a key role in Salmonella Typhimurium pathogenicity. We found that RNase G determines the half-life of hns mRNA by cleaving its 5' untranslated region and that altering its cleavage sites by genome editing stabilizes hns mRNA, thus decreasing S.

An alternative miRISC targets a cancer-associated coding sequence mutation in FOXL2.

Recent evidence suggests that animal microRNAs (miRNAs) can target coding sequences (CDSs); however, the pathophysiological importance of such targeting remains unknown. Here, we show that a somatic heterozygous missense mutation (c.402C>G; p.

FOXL2 directs DNA double-strand break repair pathways by differentially interacting with Ku.

The balance between major DNA double-strand break (DSB) repair pathways is influenced by binding of the Ku complex, a XRCC5/6 heterodimer, to DSB ends, initiating non-homologous end joining (NHEJ) but preventing additional DSB end resection and homologous recombination (HR). However, the key molecular cue for Ku recruitment to DSB sites is unknown. Here, we report that FOXL2, a forkhead family transcriptional factor, directs DSB repair pathway choice by acetylation-dependent binding to Ku.

Amine-Reactive Activated Esters of -CarboxyBODIPY: Fluorogenic Assays and Labeling of Amines, Amino Acids, and Proteins.

Fluorescence-based amine-reactive dyes are highly valuable for the sensing of amines and the labeling of biomolecules. Although it would be highly desirable, large changes in emission spectra and intensity seldom accompany the conjugation of known amine-reactive dyes to their target molecules. On the contrary, amide bond formation between amines and the pentafluorophenyl () and succinimidyl () esters of -carboxyBODIPY results in significant changes in emission maxima (Δλ: 70-100 nm) and intensity (up to 3000-fold), enabling the fast (down to 5 min) and selective fluorogenic detection and labeling of amines, amino acids, and proteins.

BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells.

The adaptor-related protein complex 5 subunit mu 1 (AP5M1) is an evolutionally conserved protein with ubiquitous expression in human tissues. However, the major function of AP5M1 in living organisms is unclear owing to few published studies. Here, we demonstrate that AP5M1 is a potent apoptosis-inducing molecule in cervical cancer cells.

Metabolic and lipidomic investigation of the antiproliferative effects of coronatine against human melanoma cells.

Melanoma is the most aggressive form of skin cancer, with metastatic melanoma being refractory to currently available conventional therapies. In this study, we evaluated the inhibitory effect of coronatine (COR) on the proliferation of metastatic melanoma cells. COR inhibited the proliferation of melanoma cells but negligibly affected the proliferation of normal melanocytes.

Divergent rRNAs as regulators of gene expression at the ribosome level.

It is generally assumed that each organism has evolved to possess a unique ribosomal RNA (rRNA) species optimal for its physiological needs. However, some organisms express divergent rRNAs, the functional roles of which remain unknown. Here, we show that ribosomes containing the most variable rRNAs, encoded by the rrnI operon (herein designated as I-ribosomes), direct the preferential translation of a subset of mRNAs in Vibrio vulnificus, enabling the rapid adaptation of bacteria to temperature and nutrient shifts.

Non-peptidic guanidinium-functionalized silica nanoparticles as selective mitochondria-targeting drug nanocarriers.

We report on the design and fabrication of a FeO core-mesoporous silica nanoparticle shell (FeO@MSNs)-based mitochondria-targeting drug nanocarrier. A guanidinium derivative (GA) was conjugated onto the FeO@MSNs as the mitochondria-targeting ligand. The fabrication of the FeO@MSNs and their functionalization with GA were carried out by the sol-gel polymerization of alkoxysilane groups.

Selective Monitoring and Imaging of Eosinophil Peroxidase Activity with a J-Aggregating Probe.

The specific detection of eosinophil peroxidase (EPO) activity requires the difficult distinction between hypobromous acid generated by EPO and hypochlorous acid generated by other haloperoxidases. Here we report a fluorogenic probe that is halogenated with high kinetic selectivity (≥1200:1) for HOBr over HOCl. Heavy-atom effects do not quench the dibrominated product because of its self-assembly into emissive J-aggregates that provide a turn-on signal.

Correction: Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting.

[This corrects the article DOI: 10.18632/oncotarget.8719.