Investigating the Effects of HMGB1 Overexpression on Colorectal Cancer Cell  Migration via Oncolytic Herpes simplex Virus Type 1 (oHSV-1)

Sara  Shayan; Arash  Arashkia; Golnaz  Bahramali; Kayhan  Azadmanesh

doi:10.18502/ajmb.v16i2.14863

Sara Shayan Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran
Arash Arashkia Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran
Golnaz Bahramali Department of Hepatitis and AIDS and Blood Borne Diseases, Pasteur Institute of Iran, Tehran, Iran
Kayhan Azadmanesh Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran

DOI: https://doi.org/10.18502/ajmb.v16i2.14863

Keywords: Colorectal neoplasms, Galectin 1, HMGB1 protein, Oncolytic virotherapy, Simple virus, Tumor microenvironment

Abstract

Background: 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.

Methods: To explore this, we developed oncolytic virotherapy, resulting in HSV-HMGB1, an oncolytic Herpes simplex virus that expresses HMGB1. HMGB1 is known its role in cancer progression, particularly in the context of cancer cell migration.

Results: 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 con-ditions was further validated using quantitative RT-PCR, aligning with the findings from our microarray data.

Conclusion: 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.