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Simple Summary: In patients with high-risk prostate cancer (HRPC) after radical prostatectomy, biochemical recurrence increases the risk of distant metastasis. Therefore, complementary prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence after biochemical recurrence. This study was performed to identify prognostic factors for clinical recurrence in patients with HRPC who experience biochemical recurrence by conducting an analysis of the expression levels of snRNAs in formalin-fixed paraffin-embedded (FFPE) radical prostatectomy samples. The FFPE sample-derived snRNA RNU1-1/RNU1-2 could serve as an independent prognostic factor of clinical recurrence-free survival after biochemical recurrence of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between patients with clinical and non-clinical recurrence. Thus, snRNAs associated with prostate cancer may assist the early detection of clinical recurrence in patients with HRPC, allowing for more tailored and restorative treatments. In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective of this study was to identify biomarkers in formalin-fixed paraffin-embedded (FFPE) RP samples that are prognostic for CR in patients with HRPC who experience BCR after RP (post-RP BCR). First, we performed a preliminary RNA sequencing analysis to comprehensively profile RNA expression in FFPE RP samples obtained from patients with HRPC who developed CR after post-RP BCR and found that many snRNAs were very abundant in preserved FFPE samples. Subsequently, we used quantitative polymerase chain reaction (qPCR) to compare the expression levels of highly abundant snRNAs in FFPE RP samples from patients with HRPC with and without CR after post-RP BCR (21 CR patients and 46 non-CR patients who had more than 5 years of follow-up after BCR). The qPCR analysis revealed that the expression levels of snRNA RNU1-1/1-2 and RNU4-1 were significantly higher in patients with CR than in patients without CR. These snRNAs were significantly correlated with clinical recurrence-free survival (RFS) in patients with HRPC who experienced post-RP BCR. Furthermore, snRNA RNU1-1/1-2 could serve as an independent prognostic factor for clinical RFS in post-RP BCR of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between CR and non-CR patients. Our findings provide new insights into the involvement of snRNAs in prostate cancer progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma is a highly malignant tumor with increasing prevalence worldwide. Extracellular vesicles exert their biological functions via the delivery of different biomolecules, including non-coding RNAs. In this review, the diverse roles of the non-coding RNA cargo of hepatocellular carcinoma-derived extracellular vesicles will be discussed. Their function in tumor progression, immune escape, and drug resistance, as well as their potentialvalue as biomarkers of disease, will be summarized. Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is a major public health problem worldwide, and it is often diagnosed at advanced stages, when no effective treatment options are available. Extracellular vesicles (EVs) are nanosized double-layer lipid vesicles containing various biomolecule cargoes, such as lipids, proteins, and nucleic acids. EVs are released from nearly all types of cells and have been shown to play an important role in cell-to-cell communication. In recent years, many studies have investigated the role of EVs in cancer, including HCC. Emerging studies have shown that EVs play primary roles in the development and progression of cancer, modulating tumor growth and metastasis formation. Moreover, it has been observed that non-coding RNAs (ncRNAs) carried by tumor cell-derived EVs promote tumorigenesis, regulating the tumor microenvironment (TME) and playing critical roles in the progression, angiogenesis, metastasis, immune escape, and drug resistance of HCC. EV-related ncRNAs can provide information regarding disease status, thus encompassing a role as biomarkers. In this review, we discuss the main roles of ncRNAs present in HCC-derived EVs, including micro(mi) RNAs, long non-coding (lnc) RNAs, and circular (circ) RNAs, and their potential clinical value as biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: tRF-27 has been identified as upregulated in both naïve trastuzumab-resistant HER2-positive breast cancer cells and patient samples, positioning it as a potential biomarker. However, the underlying mechanisms of this upregulation remain unclear. This study proposes that the abnormal transcription of specific tRNA-Cys-GCA isodecoders in naïve trastuzumab-resistant cells might contribute to the accumulation of tRF-27. Additionally, the reduction in H3K27me3 modifications at these tRNA genes, attributed to imbalances in histone modification enzymes, appears to influence tRNA transcription alterations. Building upon these findings, our research demonstrates that the application of a demethylase inhibitor may offer a potential strategy to overcome trastuzumab resistance. tRNA-derived fragments (tRFs) play crucial roles in cancer progression. Among them, tRF-27 has been identified as a key factor in promoting naïve trastuzumab resistance in HER2-positive breast cancer. However, the origin of tRF-27 remains uncertain. In this study, we propose that the upregulated expression of specific cysteine tRNAs may lead to the increased accumulation of tRF-27 in trastuzumab-resistant JIMT1 cells. Mechanistically, the reduced inhibitory H3K27me3 modification at the promoter regions of tRF-27-related tRNA genes in JIMT1 cells, potentially resulting from decreased EZH2 and increased KDM6A activity, may be a critical factor stimulating the transcriptional activity of these tRNA genes. Our research offers fresh insights into the mechanisms underlying elevated tRF-27 levels in trastuzumab-resistant breast cancer cells and suggests potential strategies to mitigate trastuzumab resistance in clinical treatments. [ABSTRACT FROM AUTHOR]

Living organisms experience a range of stresses. To cope effectively with these stresses, eukaryotic cells have evolved a sophisticated mechanism involving the formation of stress granules (SGs), which play a crucial role in protecting various types of RNA species under stress, such as mRNAs and long non‐coding RNAs (lncRNAs). SGs are non‐membranous cytoplasmic ribonucleoprotein (RNP) granules, and the RNAs they contain are translationally stalled. Importantly, SGs have been thought to contribute to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). SGs also contain multiple RNA‐binding proteins (RBPs), several of which have been implicated in AD progression. SGs are transient structures that dissipate after stress relief. However, the chronic stresses associated with aging lead to the persistent formation of SGs and subsequently to solid‐like pathological SGs, which could impair cellular RNA metabolism and also act as a nidus for the aberrant aggregation of AD‐associated proteins. In this paper, we provide a comprehensive summary of the physical basis of SG‐enriched RNAs and SG‐resident RBPs. We then review the characteristics of AD‐associated gene transcripts and their similarity to the SG‐enriched RNAs. Furthermore, we summarize and discuss the functional implications of SGs in neuronal RNA metabolism and the aberrant aggregation of AD‐associated proteins mediated by SG‐resident RBPs in the context of AD pathogenesis. Geriatr Gerontol Int 2024; 24: 7–14. [ABSTRACT FROM AUTHOR]

Background: The present research aims to investigate the clinical diagnostic value of LncRNA HOXA distal transcript antisense RNA (HOTTIP) in acute respiratory distress syndrome (ARDS) of sepsis and its predictive significance for mortality. Methods: One hundred eighteenth patients with sepsis and 96 healthy individuals were enrolled. RT-qPCR to examine HOTTIP levels. The incidence of ARDS and death was recorded. The diagnostic significance of HOTTIP in sepsis ARDS was examined using ROC and logistic regression analysis. The correlation between HOTTIP and disease severity was evaluated using Pearson's coefficients. Kaplan-Meier analysis and COX regression were employed to examine the predictive significance of mortality. Validation of HOTTIP target miRNA by dual-luciferase assay. Results: HOTTIP was persistently up-regulated in patients with ARDS sepsis than in patients without ARDS patients (P < 0.05). HOTTIP was a risk factor for the development of ARDS, which could be diagnosed in ARDS patients from non-ARDS patients (AUC = 0.847). Both the SOFA score (r = 0.6793) and the APACHE II score (r = 0.6384) were positively correlated with the HOTTIP levels. Furthermore, serum HOTTIP was an independent predictor of short-term mortality (HR = 4.813. 95%CI: 1.471–15.750, P = 0.009) and noticeably predicted the occurrence of short-term death (log rank = 0.020). miR-574-5p, a target miRNA for HOTTIP, was reduced in patients with sepsis ARDS and negatively correlated with HOTTIP. Conclusions: The presence of HOTTIP serves as a diagnostic biomarker for the occurrence of ARDS, exhibits correlation with disease severity, and provides predictive value of short-term mortality in sepsis patients. HOTTIP may be involved in ARDS progression by targeting miR-574-5p. [ABSTRACT FROM AUTHOR]

The objective of this study was to analyze the influence of long non-coding ribonucleic acid PGM5-AS1 on lung cancer cell ferroptosis through microrna-587. To this end, the research team has included the abnormal expression vectors of PGM5-AS1 and microrna-587 were transfected into human lung cancer cell line A549 to detect alterations in cell activity, apoptosis, cell cycle, oxidative stress, iron ion and ferroptosis-associated proteins. The results show silencing PGM5-AS1 or elevating microrna-587 promoted A549 proliferation and invasion, while inhibiting apoptosis and resisting ferroptosis. However, increasing PGM5-AS1 or silencing microrna-587 enhanced A549 apoptosis and induced ferroptosis (P < 0.05). And in the salvage experiment, the research team found that microrna-587 mimics inhibited PGM5-AS1-wild sequence fluorescence activity. The biological behavior of A549 after increasing (or silencing) PGM5-AS1 and microrna-587 was not different from that of cells transfected with microrna-587 negative control (P > 0.05). These results suggest that lowexpressed PGM5-AS1 can promote lung cancer cell viability, inhibit apoptosis and resist ferroptosis through targeted increase of microrna-587. [ABSTRACT FROM AUTHOR]

• MALAT1 is key for diabetic foot ulcer healing in rats. • High glucose reduces MALAT1 in stem cells, affecting ulcers. • MiR-142 regulates genes crucial for diabetic ulcer healing. • Studies show MALAT1′s role in age-related diabetic ulcers. • Stem cell therapy promising for elderly diabetic foot ulcers. Diabetic foot ulcer (DFU) is a serious diabetes complication, significantly impacting the quality of life, particularly in the elderly. Age-associated DFUs pose additional challenges due to impaired healing mechanisms. Our study aims to explore the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) as a miR-142 sponge in repairing diabetic rat foot ulcer tissue under age-associated diabetes, offering a new theoretical basis and therapeutic target for preventing and treating diabetic vascular disease in the elderly. Using qPCR, we analyzed MALAT1 and miR-142 expression in EPCs and hUC-MSCs. Targetscan predicted potential interaction targets for MALAT1 and miR-142, confirmed by dual luciferase reporter gene assay. An age-associated diabetic rat model was established using Streptozotocin (STZ) injection. Hypoxia, apoptosis, and angiogenesis-related proteins were assessed through Western Blot. In vitro, miR-142 inhibition and MALAT1 overexpression promoted foot ulcer healing in diabetic rats. MALAT1 acted as a miR-142 sponge, downregulated in hUC-MSCs under high glucose, relevant to age-associated diabetic foot ulcers. MiR-142 negatively regulated SIRT1 and Nrf2. In vitro experiments demonstrated potential significance for age-related DFU treatment. MALAT1 in human umbilical cord mesenchymal stem cells expedited foot ulcer healing in diabetic rats, particularly in age-associated diabetes, through miR-142 sponge activity. These findings offer insights for novel therapeutic strategies targeting elderly diabetic foot ulcers, emphasizing exogenous stem cell transplantation's potential in effective DFU treatment for the elderly. [Display omitted] [ABSTRACT FROM AUTHOR]