Evaluation of the HSV-۱ LAT Transcript Expression Effects on TGF-β Signaling Pathway in Human Neuroblastoma Cells

Objective: Infection with herpes simplex virus type ۱ induces viral latency in neuron trigeminal ganglions. The late associated transcript (LAT) is uniquely expressed in infected neural cells, however no coding protein associated with these transcripts has been identified in infected cells. It has been shown that six microRNAs transcribed from LAT have the capabilities to affect the cell signaling pathways, thus interfering in pathways such as those of cell differentiation and proliferation. Transforming growth factor beta (TGF-β) pathway is a critical pathway among cell signaling circuits. The Smad۴ protein, as an important member of the TGF-β signaling pathway, mediates the connection between membrane receptors, cytoplasmic kinases, and nuclear transcription factors. Methods: This study bioinformatically and experimentally evaluated LAT microRNA expression and assessed microRNA targeting of Smad۴ transcripts in human neuroblastoma cells by using real-time PCR. Results: Analysis of two different softwares results showed that the Smad۴ gene was targeted by LAT-derived microRNAs at multiple sites. Over-expression of LAT microRNAs in BE۲(c) cells caused reduction in Smad۴ transcripts. Conclusion: The results of bioinformatical analysis with relative quantification of Smad۴ transcripts and its downstream-related genes such as cyclinD, CDK۲, and Myc showed that the LAT transcript could control Smad۴ expression.

کلیدواژه ها:

microRNA ، microRNAs ، Herpes Simplex Virus-۱ ، Latency Associated Transcript ، Smad۴ Protein ، ویروس هرپس سیمپلکس تیپ یک ، رونوشت وابسته به نهفتگی ، پروتئینSmad۴