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EBioMedicine ; 51: 102583, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31901866


BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear. METHODS: The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models. FINDINGS: In contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3'-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA. INTERPRETATION: Our data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments.

Nutrition ; 58: 83-88, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30391695


OBJECTIVES: Fatty acids (FA) in human milk play an important role in meeting the nutritional demands and promoting the growth and development of breastfeeding infants. Breast milk FA is sensitive to maternal dietary habits, and dietary patterns are better used to explain the effect of diet on FA. Few studies have examined the association between maternal dietary patterns and the FA components of breast milk in developing countries. In this study, we aimed to determine whether dietary patterns affect the FA profile of breast milk in lactating Chinese mothers with the overall goal to optimize the management of infant feeding. METHODS: A total of 274 lactating women ranging from 22 d to 6 mo postpartum were included, and samples of their breast milk were collected together with completed questionnaires. Using a principal component analysis, four dietary patterns were identified in a rotated component matrix. FA profiles were detected using capillary gas chromatography and presented as the percentage by weight of total FA. RESULTS: Maternal intake of energy, carbohydrates, and proteins showed differences between the different dietary patterns. In addition, there were significant differences in the total proportions of saturated, polyunsaturated, and ω-6 polyunsaturated fatty acids in breast milk among the four patterns (P < 0.001; P = 0.025; P = 0.038, respectively). CONCLUSIONS: The results demonstrate that maternal dietary patterns can affect macronutrient intake levels and milk FA profiles in lactating Chinese women. These results are of great significance in understanding how a maternal diet can both improve maternal macronutrient intake and the FA nutritional status of breast milk.

Dieta/métodos , Ácidos Graxos/metabolismo , Leite Humano/metabolismo , Mães , Nutrientes/administração & dosagem , Adulto , China , Feminino , Humanos , Lactação , Pessoa de Meia-Idade , Análise de Componente Principal , Adulto Jovem
Biomed Environ Sci ; 30(1): 64-67, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28245901


The present study was designed to examine the contributions of the fatty acid elongase (ELOVL) gene polymorphisms to the levels of polyunsaturated fatty acids (PUFAs) in breast milk. Two hundred and nine healthy Han Chinese mothers were included in the study. Carriers of minor alleles of SNPs (rs2397142 and rs9357760) in ELOVL5 were associated with higher levels of linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), docosatetraenoic acid (DTA), docosahexenoic acid (DHA), while in rs209512 of ELOVL5 the carriers of minor alleles had lower levels of DTA compared to major homozygote alleles (P ranged from 0.004-0.046), and genetically explained variability ranged from 3.2% for eicosapentaenoic acid (EPA) to 6.0% for LA. Our findings demonstrated that common variation in ELOVL5 gene encoding rate-limiting enzymes in the metabolism of PUFAs contribute to the PUFAs in breast milk.

Acetiltransferases/genética , Ácidos Graxos Insaturados/genética , Leite Humano/química , Grupo com Ancestrais do Continente Asiático/genética , China , Feminino , Humanos , Polimorfismo de Nucleotídeo Único
Oncol Lett ; 6(3): 681-686, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24137390


Changes in filamin A (FLNa) expression contribute to the development and progression of numerous malignancies. However, in vitro studies of breast cancer have shown conflicting results. Thus, the present study aimed to detect the expression of FLNa in breast cancer tissue samples and the association with clinicopathological data, in order to provide insightful ex vivo data. A total of 96 breast cancer and distant normal breast tissues and 20 benign tumor tissue specimens were subjected to immunohistochemistry or reverse transcription polymerase chain reaction (RT-PCR) analysis of FLNa expression. Clinicopathological data were collected to analyze the association with FLNa expression. The FLNa protein was overexpressed in breast cancer tissues compared with distant normal mammary gland and benign breast tissues. The FLNa protein was expressed in 63.5% of breast cancer, with positive rates of 36, 66.7 and 84.6%, respectively, in stage I, II and III breast cancer patients (P<0.05). Overexpression of the FLNa protein was associated with advanced stage, lymph node metastasis, vascular or neural invasion, menstruation state and other risk stratifications for breast cancer. The overexpression of FLNa in breast cancer was validated by RT-PCR, indicating transcriptional regulation of FLNa overexpression in breast cancer. FLNa mRNA and protein were overexpressed in breast cancer tissues, which was associated with advanced stage, lymph node metastasis and vascular or neural invasion of breast cancer, suggesting that FLNa contributes to breast cancer development and progression.