Inflamma-miRs in Aging and Breast Cancer: Are They Reliable Players?

Abstract

Human aging is characterized by chronic low-grade inflammation known as “inflammaging.” Persistent low-level inflammation also plays a key role in all stages of breast cancer since “inflammaging” is the potential link between cancer and aging through NF-kB pathways highly influenced by specific miRs. Micro-RNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at a posttranscriptional level. Inflamma-miRs have been implicated in the regulation of immune and inflammatory responses. Their abnormal expression contributes to the chronic pro-inflammatory status documented in normal aging and major age-related diseases (ARDs), inflammaging being a significant mortality risk factor in both cases. Nevertheless, the correct diagnosis of inflammaging is difficult to make and its hidden contribution to negative health outcomes remains unknown. This methodological work flow was aimed at defining crucial unanswered questions about inflammaging that can be used to clarify aging-related miRNAs in serum and cell lines as well as their targets, thus confirming their role in aging and breast cancer tumorigenesis. Moreover, we aim to highlight the links between the pro-inflammatory mechanism underlying the cancer and aging processes and the precise function of certain miRNAs in cellular senescence (CS). In addition, miRNAs and cancer genes represent the basis for new therapeutic findings indicating that both cancer and ARDs genes are possible candidates involved in CS and vice versa. Our goal is to obtain a focused review that could facilitate future approaches in the investigation of the mechanisms by which miRNAs control the aging process by acting as efficient ARDs inflammatory biomarkers. An understanding of the sources and modulation of inflamma-miRs along with the identification of their specific target genes could enhance their therapeutic potential.

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

“…The influence of miRNA in microglia-mediated immune response was recently reviewed [83] and abnormal expression of inflamma-miRs showed them to contribute to chronic proinflammatory status and to be a significant mortality risk factor [84]. MiRNAs are small noncoding RNA molecules that are 18–25 nucleotides in length involved in the regulation of gene expression.…”

Landscape of genome-wide age-related DNA methylation in breast tissue

“…Some aDNAm’s were identified in genes for non-coding RNAs (ncRNAs) that may affect regulation of gene expression [ 25 , 26 ] and involved in breast cancer [ 27 , 28 ]. It has previously been reported that ncRNAs may be associated with aging [ 29 ]., 8 aDNAm’s were located in the promoters of precursor-miRNAs (pre-miRNAs), indicating a possible regulatory role of the aDNAm’s in miRNA expression. These include mir-15b/16–2 that targets the BCL2 oncogene [ 30 – 32 ]; mir-7-3, a let-7 family member that regulates the RAS oncogene [ 33 ]; mir-148a, known to induce apoptosis by targeting IGF-1R and IRS1 in breast cancer cells [ 34 ]; mir-426 known to promote cell proliferation in breast cancer [ 35 ]; and, mir-935 known to be differentially expressed in hormone-responsive breast cancer cells [ 36 ].…”

An Emerging Class of Long Non-coding RNA With Oncogenic Role Arises From the snoRNA Host Genes

“…In malignant diseases, the imbalance between overactivation of proto-oncogenes and inhibition of tumor suppressor genes is usually the consequence of a faulty regulatory system, which includes, among others, the non-coding RNAs (3)(4)(5). Most of these transcripts do not have the ability to interact with the ribosome and are not translated into proteins (6)(7)(8)(9)(10)(11); however, they interact with other coding or non-coding RNAs (ncRNAs), being part of complex regulatory networks (12). The ncRNAs are divided into two classes: the small ncRNAs (with <200 nt) and the long ncRNAs (lncRNAs), with >200 nt (13).…”