Waqar Ahmad

MicroRNAs (miRNAs) are small RNA molecules implicated in controlling most cellular processes by either deadenylating/degrading mRNA transcripts or inhibiti

Highlights: • Bulk RNA sequencing reveals 566 genes driving lactogenic differentiation in HC11 cells. • Hormonal (prolactin and insulin), mitogenic (ErbB), and autophagic pathway enrichment was observed. • Differentiation markers (Wap, Csn2, Lalba, and Gata3) suggest a secretory fate. • mTOR may act as a central hub integrating hormonal, mitogenic, and autophagic inputs. • These systems-level insights into lactogenic differentiation need empirical validation.

The cotton leafhopper, Amrasca biguttula Ishida (Hemiptera: Cicadellidae), is a significant pest that feeds on various host plants, particularly cotton, re

This study aimed to identify miRNA-based biomarkers in a multi-ethnic cohort of SARS-CoV-2-infected individuals to enhance preparedness for future variants of concern. A total of 31 healthy controls and 154 infected patients were enrolled, from which 13 matched controls and 38 infected nasal swab samples were analyzed using miRNA sequencing, followed by qRT-PCR validation. Among the 1788 miRNAs detected, 14 differentially expressed miRNAs and four novel miRNAs were identified, with novel-miR-264-5p showing a ≥ 2-fold change. Correlation with clinical markers highlighted several miRNAs as potential prognostic biomarkers. Seven miRNAs, including miR-146b-3p, miR-154-5p, miR-5010-3p, miR-127-3p, miR-335-3p, miR-30c-5p, and miR-202-5p, showed strong prognostic potential. Combined ROC analysis demonstrated that a panel of top-performing miRNAs significantly enhanced diagnostic accuracy (AUC 0.939–0.972; p < 0.0001). Moreover, integrating miRNA biomarkers with clinical parameters further improved performance (AUC = 0.982; p < 0.0001). miR-146b-3p, detected exclusively in infected patients, emerged as a highly specific biomarker. Several nasal miRNAs mirrored blood profiles, highlighting the utility of nasal swabs for non-invasive monitoring. Collectively, these findings suggest that miRNA-based biomarkers, alone or combined with clinical markers, offer a promising platform for COVID-19 prognosis and diagnosis, and lay groundwork for future miRNA-based antiviral strategies.

Alzheimer’s disease (AD) is associated with the formation of tau-hyperphosphorylated neurofibrillary tangles (NFTs). Impaired glucose metabolism has

The intricate interplay between viruses and hosts involves microRNAs (miRNAs) to regulate gene expression by targeting cellular/viral messenger RNAs (mRNAs). Mouse mammary tumour virus (MMTV), the aetiological agent of breast cancer and leukaemia/lymphomas in mice, provides an ideal model to explore how viral and host miRNAs interact to modulate virus replication and tumorigenesis. We previously reported dysregulation of host miRNAs in MMTV-infected mammary glands and MMTV-induced tumours, suggesting a direct interaction between MMTV and miRNAs. To explore this further, we systematically examined all potential interactions between host miRNAs and the MMTV genome using advanced prediction tools. Leveraging miRNA sequencing data from MMTV-expressing cells, we identified dysregulated miRNAs capable of targeting MMTV. Docking analysis validated the interaction of three dysregulated miRNAs with the MMTV genome, followed by confirmation with RNA immunoprecipitation assays. We further identified host targets of these miRNAs using mRNA sequencing data from MMTV-expressing cells. These findings should enhance our understanding of how MMTV replicates and interacts with the host to induce cancer in mice, a model important for cancer research. Given MMTV’s potential zoonosis and association with human breast cancer/lymphomas, if confirmed, our work could further lead to novel miRNA-based antivirals/therapeutics to prevent possible MMTV transmission and associated cancers in humans.

The mouse mammary tumor virus (MMTV) encodes a 5’ element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5’ element is Rem-responsive or has any functional interaction with host/viral factors to facilitate MMTV gene expression was tested in this study. Our results reveal that the 5’ element is non-responsive to Rem, but can be transactivated by both HIV Tat and HTLV-1 Tax activators. Reciprocally, MMTV could transactivate not only HIV TAR (similar to HTLV Tax), but also its 5’ element. Furthermore, we reveal involvement of pTEFb, a general elongation factor associated with transactivation by Tat/Tax. This makes MMTV the first betaretrovirus to encode both Rem/RRE and Tat/TAR-Tax/TRE-like transcription regulatory systems. This study should enhance not only our understanding of retrovirus replication and virally-induced cancers/immunodeficiency syndromes, but also development of improved retroviral vectors for human gene therapy.

The mouse mammary tumor virus (MMTV) induces mammary tumors in mice. Recently, we have shown that MMTV perturbs expression of the host miR-17-92 cluster in MMTV-infected mammary glands and MMTV-induced mammary tumors. Known as oncomiR-1, this cluster is often dysregulated in a number of cancers, especially breast cancer. Therefore, we investigated whether there was a functional interaction between MMTV and the cluster. Our results reveal that MMTV expression led to dysregulation of the cluster in both mammary epithelial HC11 and HEK293T cells with the expression of miR-92a cluster member being affected the most. Conversely, over-expression of the whole or partial cluster significantly repressed MMTV expression. Interestingly, overexpression of miR-92a alone resulted in MMTV repression to the same extent as observed with the whole or partial cluster. Inhibition of miR-92a led to nearly a complete recovery of MMTV gene expression. Deletion/substitution of the miR-92a seed sequence within the cluster rescued MMTV expression. Dual luciferase assays identified MMTV genomic RNA as the target of miR-92a. These results show that the miR-17-92 cluster acts as part of the cell’s well-known miRNA-based anti-viral response to thwart incoming MMTV infection. Interestingly, miR-92a expression was the least amongst cluster members in MMTV-induced breast tumors, suggesting that the elevated level of MMTV expression in tumors is due perhaps to MMTV subverting miR-92a overexpression, restricting its ability to control MMTV replication during tumorigenesis. Thus, our study provides the first evidence demonstrating the biological significance of host miRNAs in controlling MMTV replication and influencing the process of tumorigenesis. Importance: MMTV is a non-acute, slow-transforming retrovirus that causes breast cancer and lymphomas in mice. Consequently, understanding how MMTV interacts with its host can reveal critical aspects of cellular anti-viral responses and the process of tumorigenesis. This study reveals that the host miR-17-92 cluster plays an anti-viral role during MMTV infection which seems to be counteracted by MMTV during tumorigenesis. This observation is significant since MMTV-induced tumors share similarity with human breast cancer and the MMTV/mouse model is the best mammalian animal model to study breast cancer initiation, progression, and therapy. Moreover, MMTV is increasingly (though controversial) being implicated in human breast cancer, leukemias/lymphomas, and biliary cirrhosis due to its potential zoonosis into humans. Thus, if proven true, understanding how miRNAs modulate MMTV replication will be critical in appreciating how hosts miRNAs affect virus replication/tumorigenesis, and towards the development of novel miRNA-based therapeutics (e.g., anti-miRs) to thwart MMTV replication in humans.

Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is responsible for coronavirus disease of 2019 (COVID‐19) that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID‐19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS‐CoV‐2 alters the host immune response by changing host‐transcriptional machinery. MicroRNAs (miRNAs) are regarded as post‐transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS‐CoV‐2 infection. Some of this could occur as an anti‐viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro‐viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS‐CoV‐2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other co‐morbidities. Having such biomarkers can be vital in not only predicting COVID‐19 prognosis, but also the development of novel miRNA‐based anti‐virals and therapeutics which can become invaluable in case of the emergence of new viral variants with pandemic potential in the future.