Non-Coding RNA

Breast cancer remains a leading cause of cancer-related mortality worldwide, with treatment resistance and tumor heterogeneity posing major clinical challenges. MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have emerged as key players in breast cancer biology, influencing tumor initiation, progression, and therapy resistance. This narrative review synthesizes recent evidence on the involvement of miRNAs in breast cancer subtypes and their impact on treatment response. Notably, miR-155, miR-503, and miR-21 have shown potential as non-invasive biomarkers and modulators of pathways such as PI3K-Akt, MAPK, and TNF signaling. Additionally, exosomal miRNAs may reflect chemoresistance profiles and predict pathological response to neoadjuvant therapy. Emerging data also support the use of specific miRNAs to sensitize tumors to radiotherapy or modulate immune checkpoints like PD-L1 in triple-negative breast cancer. However, challenges persist regarding standardization, sample types, and study heterogeneity. Further translational research is needed to validate miRNA signatures and their utility in guiding personalized treatment. By highlighting mechanistic insights and potential clinical applications, this review aims to contribute to the ongoing efforts of integrating miRNAs into precision oncology for breast cancer.

Food is a crucial component affecting the health of individuals, which may have the potential to expand lifespan. It has been shown that a long lifespan may be related to fine-tuned autophagy. In general, suitable autophagy could play a significant role in the anti-aging biological exertion of the host. AMPK, a member of serine and threonine kinases, could play vital roles within the autophagy signaling pathway in various cells. In addition, alterations in the kinase activity of AMPK have been shown to be connected to several pathologies of aging-related diseases. Therefore, autophagy could control the lifespan-related homeostasis within the host from cells to a body via the modification of AMPK. The design of the diet and/or nutrition targeting the AMPK would be a possibility to expand the lifespan. Some analyses of the molecular biology underlying the autophagy suggest that supplementation of accurate nutraceuticals, as well as dietary restriction, mild fasting, and/or appropriate physical exercise, could modulate AMPK signaling, which may be advantageous for life extension with the alteration of autophagy. Remarkably, it has been revealed that several non-coding RNAs (ncRNAs) might also play significant roles in the regulation of autophagy. In addition, the production of some ncRNAs may be associated with the alteration of gut microbiota with certain diets. Therefore, the modulation of AMPK action with ncRNAs through choosing the relevant diet could be a therapeutic tactic for promoting longevity, which is also accompanied by a reduced risk for several aging-related diseases.

Background/Objectives: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs with potential as novel biomarkers applicable to improve diagnostic and prognostic applications. Methods: We performed a comprehensive evaluation of the snoRNA-related gene expression by qPCR using benign and tumor tissue samples associated with invasive breast carcinomas of no special type (NST). Selected candidate snoRNAs, i.e., SCARNA2, SCARNA3, SNORD15B, SNORD94, SNORA68, and SNHG1, along with RNU2-1 snRNA, were further validated and their associations with clinicopathological parameters were examined. External datasets and plasma samples were used for additional validation. Results: SCARNA2 was identified as the most promising snoRNA biomarker candidate, showing a positive association with better progression-free survival (PFS) in our data (13.3-month survival difference between low- and high-expression groups) and with both PFS and overall survival in external RNA-seq datasets. SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA were also indicated as putative tumor suppressors. SNORD94 was associated with better progression-free survival (PFS) in our data as well (12.4-month survival difference between low- and high expression groups). Greater downregulation in the low-expression tumor subgroup compared to benign samples further supports the prognostic potential of SCARNA2 and SNORD94. Evidence for SNHG1 and SNORA68 as putative oncogenes was less conclusive. Conclusions: Several small nucleolar RNAs were found to be dysregulated in breast cancer specimens, supporting their further evaluation as potential biomarkers. In particular, SCARNA2, SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA merit further investigation to determine their clinical relevance and biological roles in breast cancer.