Non-Coding RNA最新文献

Diffuse large B-cell lymphoma (DLBCL) is the most common and clinically aggressive subtype of non-Hodgkin lymphoma (NHL). While novel therapies such as rituximab and polatuzumab vedotin have led to improved outcomes, approximately 35% of patients eventually develop relapsed or refractory disease. MicroRNAs (miRNAs), a class of endogenous single-stranded RNAs approximately 22 nucleotides in length, play a pivotal role in the regulation of gene expression at the post-transcriptional level through interactions with complementary target RNAs and contribute significantly to the development, progression, and treatment response of DLBCL. Oncogenic miRNAs, such as miR-155, miR-21, and the miR-17-92 cluster, promote proliferation, survival, immune evasion, and therapy resistance by modulating pathways including PI3K/AKT, NF-κB, and MYC. Conversely, tumor-suppressive miRNAs such as miR-34a, miR-144, miR-181a, and miR-124-3p inhibit oncogene activity and enhance apoptosis, with their loss often associated with adverse outcomes. Among these, miR-155 and miR-21 are particularly well studied, playing central roles in both tumor progression and remodeling of the tumor microenvironment. This review summarizes current evidence on the biological and clinical relevance of miRNAs in DLBCL, emphasizing their diagnostic and prognostic potential.

Background/Objectives: Bone marrow mesenchymal stromal cells (MSCs) are therapeutic cells that adopt an immunomodulatory phenotype when exposed to pro-inflammatory cytokines. Recent research efforts uncovered that many therapeutic benefits of MSCs can be attributed to the secretion of extracellular vesicles (EVs) such as exosomes, small membrane vesicles of endocytic origin present in the cellular secretome. EVs' formation and release are impacted by the autophagy pathway, which recycles proteins and organelles via lysosomal degradation. Methods: To evaluate how modulation of autophagy affects properties of MSC EVs enriched in exosomes under pro-inflammatory conditions, we treated the cells with either tamoxifen (TX) or chloroquine (CQ), two drugs known to stimulate or inhibit autophagy, respectively, together with IFNγ. MSC EVs enriched in exosomes were then purified from serum-free media, and their immunoregulatory properties were evaluated ex vivo using activated CD4 T cells; small RNA sequencing was also conducted to determine EVs' microRNA content. Results: Our data indicate that MSCs treated with CQ + IFNγ yield EVs that possess somewhat higher capacity to decrease T cell proliferation compared to other EVs. Small RNA sequencing revealed that, although similar microRNAs were found in EVs isolated from all treated cells, the treatments exerted more effect on the levels of multiple microRNAs that are known to regulate either cancer or inflammation-related biological pathways in target cells. Conclusions: Overall, we conclude that the co-treatment of MSCs with TX or CQ in the presence of pro-inflammatory cytokine IFNγ has the potential to modulate microRNA content of EVs, potentially affecting biological properties of such EVs and their effect on target cells.

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.

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.

The field of non-coding RNA research is advancing at a breathtaking pace, continually uncovering new layers of regulatory complexity and functional diversity [...].

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.

Background/Objectives: Hepatocellular carcinoma (HCC) is one of the world's deadliest cancers; however, the mechanisms that contribute to its aggressiveness are poorly understood. In the recent literature, overexpression of the Chromosome 19 MicroRNA Cluster (C19MC) has been associated with an aggressive phenotype and unfavorable prognosis in HCC. However, the molecular consequences of C19MC overexpression in HCC remain poorly understood. Methods: Here, we created a constitutive C19MC-overexpressing HCC model and used two different CRISPR-engineered C19MC-overexpressing HCC models to analyze phenotype and transcriptomic changes. Results: We observed that C19MC overexpression induces cancer stem cell (CSC) phenotypic features in vitro and analyzed transcriptomic changes in genes correlating with stemness, such as NFκB and EMT. Conclusions: C19MC induces changes in HCC that are consistent with stemness and aggression, which provides a better understanding of why C19MC could be a biomarker of poor prognosis.