Musashi2 promotes the proliferation and migration of colorectal cancer by down-regulating Numb protein

Abstract

Abstract Several studies have shown that Musashi 2 (MSI2), a posttranscriptional regulator, plays an important role in cancer development. Colorectal cancer (CRC) is a common form of cancer worldwide. Recent research suggests that MSI2 may be a potential biomarker for liver metastases in patients with colorectal cancer. MSI2 is yet to be studied in terms of its biological functions and mechanisms in CRC.Results Compared to paired normal pancreas, PC tissues showed higher Musashi2 protein levels (P<0.05). IHC staining revealed the expression of MSI2 in 146 patients' colorectal cancer specimens as well as in control samples. An analysis of the correlation between MSI2 expression and clinicopathological variables was performed, which showed that MSI2 is positively associated with the UICC stage (P=0.013) , lymph node metastasis (P=0.017) and Distance metastasis (P=0.037).When MSI2 is silenced, CRC cells are suppressed in proliferation and migration, while Numb knockdown can restore normal functions as a result of downregulation of MSI2. Mechanistically, a Co-immunoprecipitation experience showed that MSI2 is structurally combined with Numb and interacts with downstream proteins (PTEN and N-Cadherin) in CRC cells. In conclusion, these findings indicated that MSI2 regulates the Numb protein, contributing to the development and progression of CRC. CRC development and progression are heavily dependent on MSI2-Numb interaction.