长链非编码RNA及其编码的微蛋白在乳腺癌中的功能及其研究进展OA北大核心CSTPCD

[Background]Breast cancer stands as a primary malignant tumor posing a significant threat to women's physical and mental well-being.Due to its molecular heterogeneity,patients often confront issues of primary or acquired drug resistance,leading to tumor recurrence and distant metastasis,the foremost causes of death among breast cancer patients.Consequently,identifying sensitive and specific early diagnostic markers,prognostic indicators,discovering safe and effective novel therapeutic targets,and overcoming drug resistance during treatment are pivotal challenges in breast cancer diagnosis and therapy.In recent years,long non-coding RNAs(lncRNAs)have garnered significant attention as key players in epigenetic regulation.Some lncRNAs contain open reading frames(ORFs)capable of encoding functional proteins.Growing research underscores the close association among lncRNAs,their encoded microproteins,and tumor initiation and progression.LncRNAs and their encoded microproteins not only regulate the expression of cancer-related genes,such as oncogenes and tumor suppressors,but also impact cancer cell proliferation,differentiation,invasion,and metastasis.Moreover,by modulating immune-related genes and the tumor microenvironment,they may influence tumor immune responses.These findings suggest the promising potential of lncRNAs and their microprotein products in the diagnosis and treatment of cancer.[Progress]This article provides a systematic review of the functions and molecular mechanisms of lncRNAs and their encoded microproteins in breast cancer.Regarding lncRNAs,we comprehensively summarize their regulatory roles in cancer progression within breast cancer.At the transcriptional level,lncRNAs can recruit specific transcription factors or chromatin-modifying factors to regulate gene transcription.At the post-transcriptional level,lncRNAs can interact with RNAs or proteins to control mRNA stability,protein translation,or N6-methyladenosine(m6A)modification,thereby playing crucial regulatory roles in breast cancer oncogenesis.Moreover,compared to protein-coding genes,lncRNAs generally exhibit tissue-specific expression patterns in vivo,making them potential biomarkers for breast cancer diagnosis,metastasis,and molecular subtyping.Their pivotal regulatory roles in breast cancer also suggest their potential as therapeutic targets.For microproteins encoded by lncRNAs,advancements in genomics,proteomics,and bioinformatics have facilitated their identification and highlighted their significant roles in human diseases,particularly cancer.Current research in breast cancer indicates that microproteins derived from lncRNAs can act as oncogenic or tumor-suppressive factors,thereby regulating the initiation and progression of breast cancer.The functional importance of lncRNAs and their encoded microproteins also suggests their potential as drug targets or diagnostic markers.[Perspective]LncRNAs and their encoded microproteins have shown great potential as noval therapeutic targets and anti-tumor drugs.However,verifying the coding potential of lncRNAs is a prerequisite for further studies on the function of micro-proteins.Accurately identifying encoded ORFs from tons of ORFs in eukaryotic genomes and distinguish them from true transcriptional or translational"noise"are great challenges.Additionally,the specific structure,localization and expression level of these microproteins still require further study,and their clinical practicability as new drug targets or biomarkers also needs to be further explored and evaluated.