Estrogen-dependent breast cancer is often treated with the aromatase inhibitors or estrogen receptor (ER) antagonists. Tamoxifen as a major ER antagonist is usually used to treat those patients with ERα-positive breast cancer. However, a majority of patients with ERα positive fail to respond to tamoxifen due to the presence of intrinsic or acquired resistance to the drug. Altered expression and functions of microRNAs (miRNAs) have been reportedly associated with tamoxifen resistance. In this study, we investigated the role of miR-27b-3p in resistance of breast cancer to tamoxifen. MiR-27b-3p levels were remarkably reduced in the tamoxifen-resistant breast cancer cells compared with their parental cells. In addition, miR-27b-3p was also significantly downregulated in breast tumor tissues relative to adjacent non-tumor tissues. Moreover, the expression levels of miR-27b-3p were lower in the breast cancer tissues from tamoxifen-resistant patients compared with that from untreated-tamoxifen patients. Notably, tamoxifen repressed miR-27b-3p expression, whereas estrogen induced miR-27b-3p expression in breast cancer cells. Besides, we provided experimental evidences that miR-27b-3p enhances the sensitivity of breast cancer cells to tamoxifen in vitro and in vivo models. More importantly, we validated that miR-27b-3p directly targeted and inhibited the expression of nuclear receptor subfamily 5 group A member 2 (NR5A2) and cAMP-response element binding protein 1 (CREB1) and therefore augmented tamoxifen-induced cytotoxicity in breast cancer. Lastly, miR-27b-3p levels were found to be significantly negatively correlated with both NR5A2 and CREB1 levels in breast cancer tissues. Our findings provided further evidence that miR-27b-3p might be considered as a novel and potential target for the diagnosis and treatment of tamoxifen-resistant breast cancer.

Abstract:Organized spatial distribution of plants (plant zonation) in salt marshes has been linked to the soil aeration condition in the rhizosphere through simplistic tidal inundation parameters. Here, a soil saturation index (ratio of saturation period to tidal period at a soil depth) is introduced to describe the soil aeration condition. This new index captures the effects of not only the tidal inundation period and frequency but also the flow dynamics of groundwater in the marsh soil. One-dimensional numerical models based on saturated flow with the Boussinesq approximations and a two-dimensional variably saturated flow model were developed to explore the behaviour of this new soil aeration variable under the influence of spring-neap tides. Simulations revealed two characteristic zones of soil aeration across the salt marsh: a relatively well aerated near-creek zone and a poorly aerated interior zone. In the near-creek zone, soils undergo periodic wetting and drying as the groundwater table fluctuates throughout the spring-neap cycle. In the interior, the soil remains largely water saturated except for neap tide periods when limited drainage occurs. Although such a change of soil aeration condition has been observed in previous numerical simulations, the soil saturation index provides a clear delineation of the zones that are separated by an 'inflexion point' on the averaged index curve. The results show how the saturation index represents the effects of soil properties, tidal parameters and marsh platform elevation on marsh soil aeration. Simulations of these combined effects have not been possible with traditional tidal inundation parameters. The saturation index can be easily derived using relatively simple models based on five non-dimensional variables.

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