Harnessing the potential of long non-coding RNAs in breast cancer: from etiology to treatment resistance and clinical applications.

Breast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related deaths of females worldwide. It is a complex and molecularly heterogeneous disease, with various subtypes that require different treatment strategies. Despite advances in high-resolution single-cell and multinomial technologies, distant metastasis and therapeutic resistance remain major challenges for BC treatment. Long non-coding RNAs (lncRNAs) are non-coding RNAs with more than 200 nucleotides in length. They act as competing endogenous RNAs (ceRNAs) to regulate post-transcriptional gene stability and modulate protein-protein, protein-DNA, and protein-RNA interactions to regulate various biological processes. Emerging evidence suggests that lncRNAs play essential roles in human cancers, including BC. In this review, we focus on the roles and mechanisms of lncRNAs in BC progression, metastasis, and treatment resistance, and discuss their potential value as therapeutic targets. Specifically, we summarize how lncRNAs are involved in the initiation and progression of BC, as well as their roles in metastasis and the development of therapeutic resistance. We also recapitulate the potential of lncRNAs as diagnostic biomarkers and discuss their potential use in personalized medicine. Finally, we provide lncRNA-based strategies to promote the prognosis of breast cancer patients in clinical settings, including the development of novel lncRNA-targeted therapies.

Gut microbiota changes associated with low-carbohydrate diet intervention for obesity.

Low-carbohydrate diets (LCDs) are frequently recommended for alleviating obesity, and the gut microbiota plays key roles in energy metabolism and weight loss. However, there is limited in-human research on how LCD changes gut microbiota. In this before-after study, 43 participants were assigned to the LCD intervention for 4 weeks. The main objective was to investigate the specific changes that occur in the participants' microbiome in response to the LCD. Changes in gut microbiota were analyzed using 16s rRNA sequencing. Body composition was measured using InBody 770. Remarkably, 35 participants (79.07%) lost more than 5% of their body weight; levels of BMI, body fat, and total cholesterol were significantly decreased, indicating the effectiveness of the LCD intervention. The richness of microbiota significantly increased after the intervention. By taking the intersection of ANOVA and linear discriminant analysis effect size (LEfSe) analysis results, we identified three phyla, three classes, four orders, five families, and six genera that were differentially enriched between baseline and week-4 time points. Among the three phyla, relative abundances of Firmicutes and Actinobacteriota decreased significantly, while Bacteroidetes increased significantly. At the genus level, Ruminococcus, Agathobacter, Streptococcus, and Bifidobacterium showed a significant reduction in relative abundances, whereas Parabacteroides and Bacteroides increased steadily. Our results demonstrate that LCD can effectively alleviate obesity and modify certain taxa of gut microbiota, providing potential insights for personalized dietary interventions against obesity.

YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths.

N6-methyladenosine (m6A) is a critical regulator in the fate of RNA, but whether and how m6A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m6A reader, YTHDF2, leading to tissue-specific programmed cell deaths (PCDs) upon fluorene-9-bisphenol (BHPF) exposure. Currently, Bisphenol A (BPA) substitutes are widely used in plastic manufacturing. Interrogating eight common BPA substitutes, we detected BHPF in 14% serum samples of pregnant participants. In a zebrafish model, BHPF caused tissue-specific PCDs triggering cardiac and vascular defects. Mechanistically, BHPF-mediated downregulation of YTHDF2 reduced YTHDF2-facilitated translation of m6A-gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m6A-sting1 decay for caudal vein plexus (CVP) apoptosis. The two distinct YTHDF2-mediated m6A regulations and context-dependent co-expression patterns of gch1/ythdf2 and tnfrsf1a/ythdf2 contributed to YTHDF2-mediated tissue-specific PCDs, uncovering a new layer of PCD regulation. Since BHPF/YTHDF2-medaited PCD defects were also observed in mammals, BHPF exposure represents a potential health threat.