Exportin-5 is an oncogene in colorectal cancer

ABSTRACT Objective: Dysregulated expression of microRNAs (miRNAs) has emerged as a hallmark feature in human cancers. Exportin-5 (XPO5), a karyopherin family member, is a key protein responsible for transporting precursor miRNAs from the nucleus to the cytoplasm. While XPO5 is one of the key regulators of miRNA biogenesis, its functional role and potential clinical significance in colorectal cancer (CRC) remains unclear. Design: The expression levels of XPO5 were initially assessed in three genomic datasets, followed by determination and validation of the relationship between XPO5 expression and clinicopathological features in two independent CRC patient cohorts. A functional characterization of XPO5 in CRC was examined by targeted gene silencing in colorectal cancer cell lines and a xenograft animal model. Results: XPO5 is upregulated, both at mRNA and protein levels, in CRCs compared with normal tissues. High-XPO5 expression associated with worse clinicopathological features and poor survival in CRC patient cohorts. The siRNA knockdown of XPO5 resulted in reduced cellular proliferation, attenuated invasion, induction of G1/S cell-cycle arrest, and downregulation of key oncogenic miRNAs in CRC cells. These findings were confirmed in a xenograft animal model wherein silencing of XPO5 resulted in the attenuation of tumor growth. Conclusion: XPO5 acts like an oncogene in CRC by regulating the expression of miRNAs and may be a potential therapeutic target in CRC.

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