MIEN1 promoter deletion leads to impaired migration and invasion potential via actin cytoskeleton rearrangement in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-associated mortality worldwide. Although early-stage CRC is responsive to surgical resection, advanced metastatic disease poses formidable treatment obstacles, triggering an alarming decline in the survival rates of patients. Hence, studying the mechanisms underlying CRC progression and identifying novel therapeutic targets are critical for early diagnosis and treatment. The migration and invasion enhancer 1 (MIEN1) protein plays a pivotal role in tumor invasion and migration across various cancer types. In CRC, the predominant upregulation of MIEN1 in cancerous tissues is closely associated with invasive behavior; however, the precise mechanism driving the metastasis remains unexplored. In this study, we investigate the role of MIEN1 in CRC by generating a CRISPR-Cas9 mediated promoter knockout in HT29 CRC cell-line. The effects of MIEN1 deletion on critical biological processes and molecular pathways, including cell adhesion, migration, and invasion, were investigated using functional assays. RNA sequencing analysis indicated alterations in actin cytoskeleton rearrangement, ultimately manifesting as differences in cellular migration and invasion potential. Signaling molecules essential for actin remodeling, such as phosphorylated FAK (pFAK-Y397) and phosphorylated cofilin (pCofilin-S3), exhibited distinct differences in their cellular localization, implicating the role of MIEN1 in modulating these key proteins. Our findings emphasize the involvement of MIEN1in diverse signaling pathways responsible for CRC migration, with its deletion leading to the disruption of several biological processes, particularly actin cytoskeleton rearrangement, which is crucial for metastasis. Therefore, targeting MIEN1 may be an effective therapeutic strategy against CRC.