OsmiR167a‐targeted auxin response factors modulate tiller angle via fine‐tuning auxin distribution in rice

Rice tiller angle determines plant growth density and further contributes grain production. Although a few genes have been characterized to regulate tiller angle in rice, the molecular mechanism underlying the control of tiller angle via microRNA is poorly understood. Here, we report that rice tiller angle is controlled by OsmiR167a‐targeted auxin response factors OsARF12, OsARF17 and OsARF25. In the overexpression of OsMIR167a plants, the expression of OsARF12, OsARF17 and OsARF25 was severely repressed and displayed larger tiller angle as well as the osarf12/osarf17 and osarf12/ osarf25 plants. In addition, those plants showed compromised abnormal auxin distribution and less sensitive to gravity. We also demonstrate that OsARF12, OsARF17 and OsARF25 function redundantly and might be involved in HSFA2D and LAZY1‐dependent asymmetric auxin distribution pathway to control rice tiller angle. Our results reveal that OsmiR167a represses its targets, OsARF12, OsARF17 and OsARF25, to control rice tiller angle by fine‐tuning auxin asymmetric distribution in shoots.     

The ubiquitin-specific protease USP2a enhances tumor progression by targeting cyclin A1 in bladder cancer

The deubiquitinating enzyme USP2a has shown oncogenic properties in many cancer types by impairing ubiquitination of FASN, MDM2, MDMX or Aurora A. Aberrant expression of USP2a has been linked to progression of human tumors, particularly prostate cancer. However, little is known about the role of USP2a or its mechanism of action in bladder cancer. Here, we provide evidence that USP2a is an oncoprotein in bladder cancer cells. Enforced expression of USP2a caused enhanced proliferation, invasion, migration and resistance to several chemotherapeutic reagents, while USP2a loss resulted in slower proliferation, greater chemosensitivity and reduced migratory/invasive capability compared with control cells. USP2a, but not a catalytically inactive mutant, enhanced proliferation in immortalized TRT-HU1 normal human bladder epithelial cells. USP2a bound to cyclin A1 and prevented cyclin A1 ubiquitination, leading to accumulation of cyclin A1 by a block in degradation. Enforced expression of wild type USP2a, but not an inactive USP2a mutant, resulted in cyclin A1 accumulation and increased cell proliferation. We conclude that USP2a impairs ubiquitination and stabilizes an important cell cycle regulator, cyclin A1, raising the possibility of USP2a targeting as a therapeutic strategy against bladder tumors in combination with chemotherapy.     

Conformational diversity of the quercetin molecule: a quantum-chemical view

Abstract

This paper focuses on the comprehensive conformational analysis of the quercetin molecule with a broad range of the therapeutic and biological actions. All possible conformers of these molecule, corresponding to the local minima on the potential energy hypersurface, have been obtained by the sequential rotation of its five hydroxyl groups and also by the rotation of its (A?+?C) and B rings relatively each other. Altogether, it was established 48 stable conformers, among which 24 conformers possess planar structure and 24 conformers – nonplanar structure. Their structural, symmetrical, energetical and polar characteristics have been investigated in details. Quantum-mechanical calculations indicate that conformers of the quercetin molecule are polar structures with a dipole moment, which varies within the range from 0.35 to 9.87 Debay for different conformers. Relative Gibbs free energies of these conformers are located within the range from 0.0 to 25.3?kcal·mol^?1 in vacuum under normal conditions. Impact of the continuum with ε?=?4 leads to the decreasing of the Gibbs free energies (–0.19–18.15?kcal·mol^?1) and increasing of the dipole moment (0.57–12.48?D). It was shown that conformers of the quercetin molecule differ from each other by the intramolecular specific contacts (two or three), stabilizing all possible conformers of the molecule – H-bonds (both classical ОН…О and so-called unusual С′Н…О and ОН…С′) and attractive van-der-Waals contacts О…О. Obtained conformational analysis for the quercetin molecule enables to provide deeper understanding of the ‘structure-function’ relationship and also to suggest its mechanisms of the therapeutic and biological actions.

Communicated by Ramaswamy H. Sarma     

Relationship between CCR2-V64I polymorphism and cancer risk: A meta-analysis

Background and objectives

The role of CCR2-V64I polymorphism in various cancers has been reported in many studies. However, results from published studies on the association between CCR2-V64I polymorphism and cancer risk are conflicting. Therefore, we performed a meta-analysis to estimate the overall cancer risk associated with the polymorphism.

Methods

Electronic searches of PubMed and EMBASE were conducted for all publications on the association between this variant and cancer. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association.

Results

Sixteen studies with 2661 cancer patients and 5801 healthy controls were included. Overall, significant association was found between the CCR2-V64I polymorphism and cancer risk (OR = 1.84, 95% CI = 1.35–2.51, AA vs GA/GG, P = 0.37). In the subgroup analysis stratified by cancer types, there was a significant association between this polymorphism and bladder cancer (OR = 2.06, 95% CI = 1.02–4.15, AA vs GA/GG, P = 0.11), cervical cancer (OR = 3.34, 95% CI = 1.48–7.50, AA vs GG, P = 0.56), and oral cancer (OR = 2.04, 95% CI = 1.46–2.84, GA vs GG, P = 0.70). In the subgroup analysis stratified by ethnicities, an increased cancer risk was also found in Europeans (OR = 2.31, 95% CI = 1.45–3.68, AA vs GA/GG, P = 0.16) and Asians (OR = 1.88, 95% CI = 1.12–3.16, AA vs GA/GG, P = 0.92).

Conclusion

This meta-analysis suggested that CCR2-V64I polymorphism may contribute to an increased risk of cancer.