As with other non-coding RNAs (ncRNAs), the aberrant expression of long non-coding RNAs (lncRNAs) can be associated with different forms of cancers, including breast cancer (BC). Various lncRNAs may either promote or suppress cell proliferation, metastasis, and other related cancer signaling pathways by interacting with other cellular machinery, thus affecting the expression of BC-related genes. However, lncRNAs are characterized by features that are unlike protein-coding genes, which pose unique challenges when it comes to their study and utility. They are highly diverse and may display contradictory functions depending on factors like the BC subtype, isoform diversity, epigenetic regulation, subcellular localization, interactions with various molecular partners, and the tumor microenvironment (TME), which contributes to the intratumoral heterogeneity and phenotypic plasticity. While lncRNAs have potential clinical utility, their functional heterogeneity coupled with a current paucity of knowledge of their functions present challenges for clinical translation. Strategies to address this heterogeneity include improving classification systems, employing CRISPR/Cas tools for functional studies, utilizing single-cell and spatial sequencing technologies, and prioritizing robust targets for therapeutic development. A comprehensive understanding of the lncRNA functional heterogeneity and context-dependent behavior is crucial for advancing BC research and precision medicine. This review discusses the sources of lncRNA heterogeneity, their implications in BC biology, and approaches to resolve knowledge gaps in order to harness lncRNAs for clinical applications.

Studies have widely indicated that the composition of maternal nutrition and diets might affect offspring health later in life. Studies on paternal contribution to the offspring’s disease are relatively scarce but are an important subject to the field. Recent research has suggested that paternal factors influenced by nutrition have been implicated in the transgenerational heritage of health and diseases through epigenetic mechanisms. This review aims to explore the current state of knowledge on nutrition-based paternal impacts on gynecological disease through epigenetics, focusing on the transmission of cancer and metabolic diseases from father to female offspring. We will explore the various mechanisms by which epigenetic landmarks, such as DNA methylation, histone modifications, and non-coding RNAs, are passed on through sperm and reprogrammed in the embryo, influencing offspring development and health. We will discuss the impacts of preconception paternal nutrition on two common cancer such as breast cancer and ovarian cancer in female offspring. Additionally, paternal overweight or obesity has been associated with increased risk of obesity in the offspring and compromised metabolic health, which may link to reproductive conditions such as infertility. Understanding the molecular mechanisms underlying non-genetic inheritance is crucial for elucidating the nutrition-mediated developmental origins of health and disease. This review highlights the mechanistic correlation between preconception paternal nutrition and female offspring gynecological health. Furthermore, it emphasizes the need for additional research to establish evidence-based paternal nutrition consultation and guidelines aimed at optimizing reproductive health and pregnancy outcomes in couples planning to conceive.