Abstract MicroRNAs (miRNA, miRs) are small noncoding RNAs that are ubiquitously expressed in all mammalian cells. Their primary function is the regulation of nascent RNA transcripts by direct binding to regions on the target. There is now exciting data to suggest that these miRNAs can bind to other miRNAs, and this may have a broader impact on gene regulation in disease states. The oncomiR miR-21 is one of the highest-expressing miRNAs in cancer cells, and in this study, we characterise which miRNAs could be potential targets of miR-21. In cancer cells delivered with a miR-21 mimic, there was an observable shift of the miRNA milieu. We demonstrate that the miR-17-92a cluster, which harbours six miRNA members, may be a target of miR-21 regulation. Additionally, the primary transcript of miR-17-92a was reduced in the presence of miR-21. In the broader context of gene regulation, overexpression of miR-21 shifted the expression of more than 150 miRNAs, including those known to regulate genes encoding proteins in cancer pathways such as the MAPK signalling and FoxO pathways. This study expands upon our limited understanding of miR:miR regulatory network and reinforces the concept that miRNAs can regulate each other, thereby influencing broader gene regulatory networks.
Abstract Background In Southeast Asia, the epidemiological profile of Head and Neck Cancer (HNC) remains under-researched. This study delineates the incidence and subtype-specific burdens of HNC in Ho Chi Minh City, Vietnam (1996–2015). Methods We conducted a population-based retrospective analysis using the Ho Chi Minh City Cancer Registry. The study estimated the 5-year point incidence for four HNC subtypes over 20 years. Age-standardised rates (ASR) were determined using national population metrics. Joinpoint regression analysis was executed to discern patterns over time. Results HNC incidence in Ho Chi Minh City escalated between 1996 and 2015, with nasopharyngeal and oral cancers demonstrating pronounced prevalence. Male diagnoses constituted 73%. The median age of HNC diagnosis in the Vietnamese cohort was approximately a decade earlier than global averages. Conclusions The marked variance in HNC trends in Ho Chi Minh City from global patterns underscores the urgency for implementing effective healthcare strategies in Vietnam.
Parasitic worms (helminths) establish chronic infection within mammalian hosts by strategically regulating their host's immune responses. Deciphering the mechanisms by which host non-coding RNAs (ncRNA) co-ordinate the activation and regulation of immune cells is essential to understanding host immunity and immune-related pathology. It is also important to comprehend how pathogens secrete specific ncRNAs to manipulate gene expression of host immune cells and influence their response to infection. To investigate the contribution of both host and helminth derived ncRNAs to the activation and/or regulation of innate immune responses during a parasite infection, we examined ncRNA expression in the peritoneal macrophages from mice infected with
Abstract Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high‐risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV‐driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridization and polymerase chain reaction (PCR) techniques, notably reverse transcription‐quantitative PCR (RT‐qPCR), offer sensitive HPV detection. Liquid‐based RT‐qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost‐effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes.
Abstract In our study, we discovered the presence of tunnelling nanotubes (TNTs) in three oral carcinoma cell lines, suggesting an alternative form of cellular communication. These TNTs act as channels for the movement of membrane-bound vesicles and microRNAs (miRNAs), indicating their potential influence on cancer progression and intercellular interactions. Our findings demonstrate that TNTs can form spontaneously under normal growth conditions, not just as a stress response. Through time-lapse microscopy, we captured the rapid and dynamic process of TNT formation, typically occurring within 20-40 minutes, via two primary methods: actin-driven cellular extensions and sustained connectivity during cell division. We also successfully visualised the active transfer of miRNA mimics through these TNTs. Notably, we detected the presence of AGO2 protein within the TNTs, implying its involvement in the delivery of miRNAs to recipient cells. Our study adds to the overall understanding of TNTs in the context of oral cancer biology and suggests a broader role for these structures in molecular transport.
Abstract Head and neck cancers, particularly oropharyngeal cancers (OPC), have been increasingly associated with human papillomavirus (HPV) infections, specifically HPV16. The current methods for HPV16 detection primarily rely on p16 staining or PCR techniques. However, it is important to note the limitations of conventional PCR, as the presence of viral DNA does not always indicate an ongoing viral infection. Moreover, these tests heavily rely on the availability of tissue samples, which can present challenges in certain situations. In this study, we developed a RT-qPCR biplex approach to detect HPV16 oncogenes E6 and E7 RNA in saliva samples from OPC patients. Salivary supernatant was used as the liquid biopsy source. We successfully obtained RNA from salivary supernatant, preserving its integrity as indicated by the detection of several housekeeping genes. Our biplex approach accurately detected E6 and E7 RNA in HPV16-positive cell lines, tissues, and finally in OPC salivary samples. Importantly, the assay specifically targeted HPV16 and not HPV18. This biplexing technique allowed for reduced sample input without compromising specificity. In summary, our approach demonstrates the potential to detect viable HPV16 in saliva from OPC patients. Since the assay measures HPV16 RNA, it provides insights into the transcriptional activity of the virus. This could guide clinical decision-making and treatment planning for individuals with HPV-related OPC.
We have previously identified a parasite‐derived peptide, FhHDM‐1, that prevented the progression of diabetes in nonobese diabetic (NOD) mice. Disease prevention was mediated by the activation of the PI3K/Akt pathway to promote β ‐cell survival and metabolism without inducing proliferation. To determine the molecular mechanisms driving the antidiabetogenic effects of FhHDM‐1, miRNA:mRNA interactions and in silico predictions of the gene networks were characterised in β ‐cells, which were exposed to the proinflammatory cytokines that mediate β ‐cell destruction in Type 1 diabetes (T1D), in the presence and absence of FhHDM‐1. The predicted gene targets of miRNAs differentially regulated by FhHDM‐1 mapped to the biological pathways that regulate β ‐cell biology. Six miRNAs were identified as important nodes in the regulation of PI3K/Akt signaling. Additionally, IGF‐2 was identified as a miRNA gene target that mediated the beneficial effects of FhHDM‐1 on β ‐cells. The findings provide a putative mechanism by which FhHDM‐1 positively impacts β ‐cells to permanently prevent diabetes. As β ‐cell death/dysfunction underlies diabetes development, FhHDM‐1 opens new therapeutic avenues.
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