Shayan Sara, Arashkia Arash, Bahramali Golnaz, Azadmanesh Kayhan
Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran.
Department of Hepatitis and AIDS and Blood Borne Diseases, Pasteur Institute of Iran, Tehran, Iran.
Avicenna J Med Biotechnol. 2024 Apr-Jun;16(2):120-129. doi: 10.18502/ajmb.v16i2.14863.
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.
To explore this, we developed oncolytic virotherapy, resulting in HSVHMGB1, an oncolytic virus that expresses HMGB1. HMGB1 is known its role in cancer progression, particularly in the context of cancer cell migration.
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.
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.
结直肠癌（CRC）是一项重大的全球健康挑战，其进展、对治疗的抗性和转移受到肿瘤微环境的强烈影响，包括缺氧等因素。本研究探讨高迁移率族蛋白B1（HMGB1）过表达对CRC细胞迁移的影响，同时鉴定与此过程相关的潜在基因。
为了探究这一点，我们开发了溶瘤病毒疗法，得到了HSV-HMGB1，一种表达HMGB1的溶瘤病毒。HMGB1在癌症进展中所起的作用已为人所知，特别是在癌细胞迁移方面。
与预期相反，我们的划痕试验表明HSV-HMGB1并未显著诱导CRC细胞迁移，这表明HMGB1可能并未直接促成这一过程。我们利用微阵列分析研究了与CRC细胞迁移相关的基因表达变化，构建了蛋白质-蛋白质相互作用（PPI）网络。该网络揭示了枢纽蛋白的存在，包括NDRG1、LGALS1和ANGPTL4，它们在癌细胞迁移中的作用已得到认可。使用定量RT-PCR进一步验证了这些基因在缺氧条件下的差异表达，与我们微阵列数据的结果一致。
我们的研究结果强调了CRC细胞迁移的复杂调控，并为潜在的分子机制和途径提供了有价值的见解。这些发现对癌症进展的进一步研究和治疗策略的开发具有启示意义。
