Non-Coding RNA

Background: Transposable elements are normally silenced by epigenetic mechanisms; however, during malignant transformation, epigenetic alterations enable transposons to produce functional molecules like miRNAs. Among these, LINE-2 (L2) elements can generate miRNAs capable of regulating key genes, including tumor suppressors. Two L2-derived miRNAs, miR-28 and miR-708, have been linked to lung cancer, yet the mechanisms underlying their dysregulation remain poorly understood. Our study reveals how genomic context contributes to aberrant gene expression through comprehensive bioinformatic analyses. Methods: Using bioinformatics analysis, we evaluated the expression of miR-28 and miR-708 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) datasets from TCGA. Further, we assessed the expression and methylation status of miR-28 and miR-708 host genes, LPP and TENM4, respectively, TENM4 using computational tools. Finaly, we searched for potential candidate tumor suppressor genes targeted by miR-28 and miR-708, which are downregulated in LUAD and LUSC. Results: We found that intragenic L2-derived miR-28 and miR-708 are significantly upregulated in LUAD and LUSC. While TENM4 gene also displays a marked increase in expression in LUAD and LUSC, in tumor versus normal tissue, this difference is less obvious for the LPP gene. We suggest that such dysregulations in expression might be linked to specific methylation patterns of their genomic locations. Furthermore, we emphasize that miR-28 and miR-708 might contribute to lung cancer pathogenesis by targeting key tumor suppressor genes. Conclusions: Alterations in the methylation status of L2-miRNAs genomic loci might result in elevated levels of miRNAs and subsequent targeting of tumor suppressor genes with potential implications in lung cancer pathogenesis.

Bone metastasis is a common and severe complication in advanced stages of breast cancer (BC) that is characterised by limited treatment options and poor patient prognosis. MicroRNAs (miRNAs) are a large class of regulatory small non-coding RNAs (ncRNAs) expressed by cells. Moreover, miRNAs can be released by cells into the blood and lymphatic streams, acting as distant cell-to-cell communicators. Of note, miRNAs have pivotal roles in the metastatic progression of BC to bone. This review summarises the most recent findings on miRNAs and their mRNA targets in driving BC bone metastasis. Furthermore, the potential clinical uses of miRNAs as future therapeutic targets/agents or biomarkers for BC bone metastasis are discussed.

CARINH is an intriguing long noncoding RNA whose unique regulatory functions intersect the seemingly distinct processes of innate immunity and cancer development. Notably, CARINH is conserved across species, offering powerful experimental models for uncovering its mechanistic roles and physiological functions across diverse biological contexts. Stimulated by interferons and viral infections, CARINH stands out as a key player in the body’s antiviral defense mechanisms. Additionally, its dysregulation has been implicated in autoimmune disorders such as psoriasis, asthma, and inflammatory bowel disease, underscoring its broader role in maintaining immune homeostasis. Furthermore, alterations in CARINH expression have been connected to cancer progression, highlighting its dual role in immune response and tumor suppression. In this review, we delve into CARINH’s pivotal function in modulating interferon responses and influencing cancer development, with a focus on the molecular pathways that regulate its expression and contribute to its diverse roles. Understanding these pathways is crucial for evaluating CARINH’s significance as a biomarker and therapeutic target, potentially leading to groundbreaking advancements in medical research and treatment strategies.