Objective: The mechanism underlying postnatal growth failure and catch-up growth in small-for-gestational-age (SGA) children is poorly understood. This study investigated the exosomal miRNA signature associated with catch-up growth in SGA children. Methods: In total, 16 SGA and 10 appropriate-for-gestational-age (AGA) children were included. Serum exosomal miRNA was analyzed using next-generation sequencing (NGS). Exosomal miRNA was profiled for five SGA children with catch-up growth (SGA-CU), six SGA children without CU growth (SGA-nCU), and five AGA children. Results: Exosomal miRNA profiles were clustered into three clear groups. The exosomal miRNA expression profiles of the SGA-nCU group differed from those of the SGA-CU and AGA groups. In all, 22 miRNAs were differentially expressed between SGA-nCU and AGA, 19 between SGA-nCU and SGA-CU, and only 6 between SGA-CU and AGA. In both SGA-nCU and SGA-CU, miR-874-3p was upregulated and miR-6126 was downregulated. Therefore, these two miRNAs could serve as biomarkers for SGA. Compared with SGA-CU and AGA, miR-30c-5p, miR-363-3p, miR-29a-3p, and miR-29c-3p were upregulated in SGA-nCU, while miR-629-5p and miR-23a-5p were downregulated. These six miRNAs could be associated with growth failure in SGA-nCU children. Conclusions: SGA children without CU have a distinct exosomal miRNA expression profile compared with AGA and SGA children with CU. Exosomal miRNAs could serve as novel biomarkers for CU.

Heavy metal exposure is increasingly linked to impaired childhood growth, but the biological mechanisms are poorly understood. Here, we assessed associations between heavy metal exposure and growth impairment (idiopathic short stature [ISS] and growth hormone deficiency [GHD]) in 36 children (24 cases, 12 controls, males 41.7%), identifying related alterations in circulating exosomal miRNAs. Blood/urine concentrations of nine metals, including Pb, As, and Hg were measured, and serum exosomal miRNAs were profiled via sequencing. Elevated heavy metal exposure was associated with significantly increased proportions of ISS and GHD. Specifically, high blood Pb was associated with ISS (p = 0.01) and high urinary As with overall short stature (p = 0.03). Elevated urinary Hg showed a marginal association with GHD (p = 0.07). Differentially expressed miRNAs were identified: hsa-miR-4488 was downregulated in high-Pb and ISS groups, whereas hsa-miR-133a-3p and hsa-miR-4516 were upregulated in high urinary Hg/As and GHD groups. Predicted targets of these miRNAs involved growth hormone (GH)–insulin-like growth factor-1 (IGF-1) signaling and endochondral ossification. In conclusion, Pb, As, and Hg exposures were associated with impaired growth in children. The dysregulation of related miRNAs suggests biological mechanisms involving both local growth-plate dysfunction and GH-IGF1 signaling disruption.

Purpose: Prostate cancer is one of the most common malignancies in men, yet current prognostic methods remain suboptimal. Emerging evidence indicates that microRNAs (miRNAs) play critical roles in prostate cancer progression. This study aimed to identify miRNAs associated with adverse clinical outcomes by comparing miRNA expression profiles between prostate tumors with unfavorable versus favorable prognostic features. Materials and Methods: High-throughput next-generation sequencing (NGS) was used to analyze miRNA expression in formalin-fixed, paraffin-embedded prostate cancer tissue samples. Patients were classified into favorable or unfavorable prognosis groups based on risk stratification scores, Gleason grade group, and biochemical recurrence. Differentially expressed miRNAs were identified using a fold-change threshold ≥2 and a false discovery rate (FDR) <0.05. Predicted target genes and pathway analyses were conducted to generate candidate regulatory hypotheses rather than confirm mechanistic relationships. Results: Several miRNAs were differentially expressed according to prognostic category. miR-206 was significantly downregulated in high-risk tumors compared with low-risk tumors. High-Gleason-grade tumors showed reduced expression of miR-7704 and miR-4454, while miR-25-3p and let-7f-5p were upregulated. In patients with early biochemical recurrence, miR-7704 and miR-10400-5p were downregulated relative to those with prolonged recurrence-free survival. Target prediction analysis identified CPEB3, HAND1, PTAR1, and SPRYD4 as shared candidate targets, with CPEB3 emerging as a prioritized candidate supported by consistency in external datasets rather than a confirmed molecular target. Conclusions: Distinct miRNA expression patterns correlate with prostate cancer aggressiveness and clinical outcomes. miR-206, miR-7704, miR-4454, miR-25-3p, and let-7f-5p represent candidate prognostic biomarkers. Their shared target CPEB3 should be interpreted as a prioritized candidate for future investigation. Given the very small sample size and the lack of qRT-PCR and functional validation, these findings should be considered preliminary and hypothesis-generating, requiring validation in larger independent cohorts and experimental studies.

Background/Objectives: This NGS-based study sought to identify novel molecular markers for prostate cancer by comparing miRNA expression in cancer and benign prostatic hyperplasia (BPH) tissues. Methods: Using high-throughput sequencing and stringent statistical criteria, the study identified eleven significantly dysregulated miRNAs (five downregulated, six upregulated) that differentiate the two conditions. Enrichment analyses linked these miRNAs to several key cancer-associated pathways, including PI3K–Akt and ErbB signaling. Results: Crucially, the protein vesicle-associated membrane protein-associated protein B (VAPB) was pinpointed as a central hub, regulated by three downregulated miRNAs (miR-143-3p, miR-221-3p, and miR-222-3p). Since VAPB has not been widely studied in prostate cancer, it represents a promising, novel candidate for both diagnosis and therapeutic targeting. Conclusions: Our NGS-based analysis revealed a distinct miRNA expression signature that differentiates prostate cancer from BPH. The downregulation of several tumor-suppressive miRNAs (with concomitant upregulation of oncogenic miRNAs) in prostate cancer may contribute to malignancy—including the de-repression of novel targets like VAPB, which we identify as a promising new biomarker and therapeutic target.

Background/Objectives: Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men. While localized PCa carries a favorable prognosis, progression to locally advanced disease substantially worsens outcomes. There is an unmet need for molecular markers that reliably distinguish indolent from aggressive tumors. MicroRNAs (miRNAs), small non-coding RNAs that post-transcriptionally regulate gene expression, are implicated in cancer development and progression, and their expression profiles may serve as putative biomarkers of disease stage. Methods: We performed small RNA sequencing on formalin-fixed paraffin-embedded (FFPE) prostate tumor tissues from nine patients (five localized, four locally advanced-stage). Differentially expressed miRNAs were identified using a bioinformatics pipeline (fold-change ≥ 2, p < 0.05). Target gene prediction, KEGG pathway enrichment, and miRNA–mRNA interaction network analyses were conducted, followed by in silico validation using two independent public mRNA datasets (GSE46602 and GSE21034, a subseries of GSE21032). Results: Seven unique mature miRNAs were differentially expressed between localized and locally advanced PCa. Five miRNAs (miR-145-5p, miR-205-5p, miR-206, miR-24-1-5p, and hsa-miR-3648) were downregulated in locally advanced tumors, while hsa-miR-625-3p and miR-324-5p were upregulated. Network analysis identified CLTC and CDK6 as putative downstream targets co-targeted by multiple downregulated miRNAs. Independent validation using GSE46602 and GSE21034 consistently demonstrated significantly higher expression of CLTC and CDK6 in locally advanced prostate cancer following Benjamini–Hochberg correction. Conclusions: This exploratory pilot analysis identified several miRNAs that differ between localized (pT2) and locally advanced (pT3–T4/N+) prostate cancer. Independent validation across two publicly available mRNA cohorts supports CLTC and CDK6 as candidate stage-associated genes. However, these findings remain hypothesis-generating and require validation in larger prospective cohorts together with functional confirmation before biomarker or therapeutic claims can be made.