Avicenna J Med Biotech arij002 Avicenna Journal of Medical Biotechnology 2008-2835 2008-4625 Avicenna Research Institute ajmb60575 Investigating the Effects of HMGB1 Overexpression on Colorectal Cancer Cell Migration via Oncolytic Herpes simplex Virus Type 1 (oHSV-1) ShayanSaraArashkiaArashBahramaliGolnazAzadmaneshKayhanDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 16 2 120 129 23 9 2023 25 11 2023

<p style="text-align:justify"><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Background:</span></strong><span style="font-size:10.0pt"> Colorectal Cancer (CRC) represents a significant global health challenge, and its progression, resistance to therapy, and metastasis are strongly influenced by the tumor microenvironment, including factors like hypoxia. This study explores the impact of High Mobility Group Box 1 (HMGB1) overexpression on CRC cell migration, while identifying potential genes associated with this process. </span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Methods:</span></strong><span style="font-size:10.0pt"> To explore this, we developed oncolytic virotherapy, resulting in HSV-HMGB1, an oncolytic <em>Herpes simplex</em> virus that expresses HMGB1. HMGB1 is known its role in cancer progression, particularly in the context of cancer cell migration. </span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Results:</span></strong><span style="font-size:10.0pt"> Contrary to expectations, our scratch assays indicated that HSV-HMGB1 did not significantly induce migration in CRC cells, suggesting that HMGB1 might not directly contribute to this process. Employing microarray analysis, we investigated gene expression changes linked to CRC cell migration, leading to construction of a Protein-Protein Interaction (PPI) network. This network revealed the presence of hub proteins, including as NDRG1, LGALS1, and ANGPTL4, which are recognized for their roles in cancer cell migration. The differential expression of these genes under hypoxic conditions was further validated using quantitative RT-PCR, aligning with the findings from our microarray data.&nbsp; </span></span></p> <p style="text-align:justify"><span style="font-size:11pt"><strong><span style="font-size:10.0pt">Conclusion:</span></strong><span style="font-size:10.0pt"> Our findings emphasize the complex regulation of CRC cell migration, and provides valuable insights into potential molecular mechanisms and pathways. These findings have implications for further research into cancer progression and the development of therapeutic strategies.</span></span></p>