Objective: We aimed at studying the mechanism of MOB1 inhibiting the proliferation and metastasis of colorectal cancer (CRC), to provide a new guidance for the early diagnosis and treatment of CRC.
Methods: MOB1 expression level in 68 pairs of CRC tissues and adjacent ones was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and the associations between the expression level of MOB1 and the clinicopathological indicators as well as the prognosis of CRC patients were analyzed. After constructing CRC cell lines that stably overexpressing or silencing MOB1, the changes of cell proliferation and metastasis ability were examined by Cell Counting Kit (CCK-8) and Transwell assay. In addition, the interaction between MOB1 and PAK2 and how the these two genes affect the biological functions of CRC cell lines were investigated by luciferase assay, qRT-PCR and Western Blot experiments.
Results: Our data showed that MOB1 expression level in CRC tissues was remarkably lower than that in adjacent ones. In comparison to patients of the group of high MOB1 expression, these patients of low MOB1 expression group showed higher incidence of distant or lymph node metastasis and lower survival rate. Cell functional experiments revealed that overexpression of MOB1 markedly attenuated the proliferation and migration ability of CRC cell lines compared to the NC group; In contrast, knockdown of MOB1 enhanced the above-mentioned cell abilities compared to anti-NC group. Luciferase assay verified an interaction between MOB1 and PAK2; and Western blot analysis showed a negative correlation between the expression of the MOB1 and PAK2 protein levels in CRC tissues. Subsequently, we demonstrated that MOB1 interacted with PAK2 to regulate its expression and affected the proliferation and migration capacity of CRC cell lines in vitro.
Conclusion: In summary, the lowly expressed MOB1 in CRC tissues and cell lines may accelerate the proliferation and migration through modulating PAK2 expression.
Keywords: MOB1, PAK2, CRC, malignant progression