Curcumol inhibits breast cancer growth via NCL/ERα36 and the PI3K/AKT pathway.

Background: Breast cancer (BC) is the most common malignancy worldwide. ERα36 (ERα66 variant) is expressed in many breast cancer cells, especially highly expressed in tamoxifen (TAM)-resistant cell lines and triple-negative breast cancer, and our previous work revealed that nucleolin (NCL) is a protein target of curcumol. This study is aimed at investigating the effect and mechanism of curcumol on ERα36 positive breast cancer cells, and the relationship between curcumol's target protein NCL and ERα36. Study design: Application of in vivo and in vitro studies to reveal the mechanism of curcumol in inhibiting BC growth and the relationship between curcumol's target protein NCL and ERα36. Methods: The anti-tumor effect of curcumol was quantified via an MTT assay, colony formation and cycle arrest, respectively. The expressions of ERα36, NCL and the proteins involved in PI3K/AKT signaling were evaluated by western blotting. The interaction between two proteins was detected using co-immunoprecipitation (Co-IP) and an immunofluorescence assay. A mouse xenograft model was established to verify the role of ERα36 in breast cancer cells and curcumol's effect on ERα36 positive cancer cells. Results: Curcumol inhibited the cell growth, caused cell cycle arrest, decreased cell cycle related proteins and inactivated the PI3K/AKT pathway in ERα36 positive breast cancer cells. There is a positive correlation between NCL and ERα36 in breast cancer cells. In addition, ERα36 bound to NCL; the two proteins were distributed in the nucleus, cytoplasm and plasma membrane, where their expression was obviously decreased by curcumol. Moreover, NCL silenced by NCL siRNA blocked the cell cycle progress and inhibited the activation of PI3K/AKT in MDA-MB-231 cells, while overexpressed ERα36 increased the expression of NCL, promoted the cell cycle progress and enhanced the activity of PI3K/AKT in MCF-7 cells. NCL knockdown or ERα36 overexpression attenuated the effect of curcumol on breast cancer cells. Conclusion: Curcumol reduced the proliferation of breast cancer cells by targeting NCL/ERα36 and inactivating the PI3K/AKT pathway.

Transcriptomic and proteomic screening of key pathways of mogroside V relieving OVA-induced mouse asthma / 中国药理学通报

Aim To discuss the potential key mechanism of mogroside V in relieving pulmonary inflammation in asthmatic mice based on transcriptomics and proteomics. Methods Ovalbumin(OVA)was chosen to induce female BALB/C mouse asthma model, and the mice were treated with mogroside V to observe the pathological changes of lung tissues. Lung tissues in groups of natural control, ovalbumin control and mogroside V control were chosen for transcriptomic and proteomic analysis, and differential genes and proteins were screened for tendency analysis, followed by KEGG enrichment analysis for the potential genes and proteins. Results The results of lung morphological observation and HE revealed that mogroside V attenuated the OVA-induced pulmonary inflammation. Differential genes and proteins were selected from RNA-seq and DIA analysis. In the analysis of omics 454 genes increased in comparison between groups of natural control with ovalbumin control and decreased in comparison between groups of mogroside V control with ovalbumin control in 1 122 potential genes, and 111 genes were of opposite features. A total of 238 proteins increased in comparison between groups of natural control with ovalbumin control and decreased in comparison between groups of mogroside V control with ovalbumin control in 497 potential proteins, and 91 proteins were of opposite features. The PI3K/Akt signaling pathway was enriched from KEGG and tendency analysis of transcriptomics and proteomics. The key factors of Igha, Ighg1, PI3K and Akt increased in ovalbumin control group and decreased in mogroside V control group by the validation of molecualr biology experiments. Conclusions Transcriptomic and proteomic analysis exhibits that mogroside V relieves asthma in mice through inhibiting the activation of key factors including Lgha, Lgh1, PI3K and Akt, depressing the signaling pathway, attenuating pulmonary inflammation to reach the goal of moistening lung and relieve cough, which provides a reference for drug development of asthma.

[Identification and analysis of the NAC transcription factor family in Triticum urartu].

NAC transcription factors are one of plant-specific gene families with diverse functions, and they regulate plant development, organ formation and stress responses. Currently, the researches about NAC transcription factors mainly focus on model plants, Arabidopsis and rice, whereas such studies are hardly reported in wheat and other plants. In this study, the full-length coding sequences (CDS) of NAC transcription factors from Triticum urartu (TuNAC) were identified through bioinformatic analysis. Their biological function, evolutionary relationship, gene duplication and chromosomal locations were further predicted and analyzed. The quantitative real-time PCR (qRT-PCR) assay was used to verify the expression pattern of abiotic-related TuNAC transcription factors. A total of 87 TuNAC transcription factors with full-length CDS were identified, which were divided into seven subgroups through phylogenetic analysis. Thirty-nine TuNAC transcription factors were located on seven chromosomes, and five pairs of TuNAC transcription factors were duplicated. The expression of four TuNAC transcription factors was consistently increased under diverse abiotic stress by qRT-PCR assay. Our study thus provides basis for further functional investigations of TuNAC transcription factors.