Abstract
As the third most common type of cancer globally, colorectal cancer (CC) is a prevalent digestive malignancy, with the second highest mortality rate among all types of cancer. It has been reported that microtubule interacting and trafficking domain containing 1 (MITD1) serves a pivotal role in the initiation and progression of diverse types of tumors. Nevertheless, the underlying mechanism of MITD1 in CC has not been previously investigated. The ENCORI and GEPIA databases were used to investigate the expression levels of MITD1 in patients with CC. Immunohistochemistry was used to detect the expression of MITD1 in cancer tissues obtained from patients with CC, while its mRNA and protein expression levels in CC cell lines were determined by reverse transcription-quantitative PCR and western blot analysis, respectively. Subsequently, MITD1 was knocked down in CC cells using an interference plasmid and Cell Counting Kit 8, colony formation, as well as EdU assays were performed to assess cell proliferation. Concurrently, wound healing and Transwell assays were performed to evaluate the migration and invasion abilities of CC cells. Lipid reactive oxygen species (ROS) levels were determined by BODIPY 581/591 C11 staining. In addition, the levels of oxidative stress markers and those of total iron were measured using the corresponding kits. Furthermore, the association between serine and arginine rich splicing factor 1 (SRSF1) and MITD1 was verified by RNA immunoprecipitation and actinomycin D experiments. Finally, to further uncover the mechanism of MITD1, SRSF1 was overexpressed and MITD1 was silenced in CC cells. The results demonstrated that the expression of MITD1 was abnormally elevated in CC tissues and CC cell lines. MITD1 silencing distinctly diminished CC cell viability, increased CC cell ferroptosis and attenuated their invasion and migration abilities. In addition, MITD1 knockdown significantly increased the expression of lipid ROS and total iron levels in CC cells. Additionally, the results showed that SRSF1 could stabilize MITD1 mRNA expression in CC cells. Finally, it was revealed that SRSF1 could regulate MITD1 and affect the progression of CC and ferroptosis via p53/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling. Overall, the results of the current study indicated that SRSF1-regulated MITD1 could affect CC progression and ferroptosis, probably via the p53/SLC7A11/GPX4 signaling pathway.