Abstract
KH-type splicing regulatory protein (KHSRP) is an RNA-binding protein implicated in a variety of cellular processes, including splicing in the nucleus and mRNA localization and degradation in the cytoplasm. The present study reports that KHSRP promotes invasiveness and metastasis of pancreatic cancer cells. KHSRP was localized in the nucleus and cell protrusions of pancreatic cancer cell lines. Suppression of KHSRP by small interfering RNA decreased the number of cell protrusions and inhibited invasiveness and metastasis of pancreatic cancer cells. KHSRP was localized in cytoplasmic RNA granules in pancreatic cancer cells, and RNA immunoprecipitation-sequencing analysis showed that the majority of enriched RNAs that immunoprecipitated with KHSRP were small nucleolar RNAs (snoRNAs). Specific KHSRP-bound snoRNAs, SNORA18 and SNORA22, associated with formation of cell protrusions. Consequently, SNORA18 and SNORA22 contributed to cell invasiveness and tumor metastasis. Our results provide insight into the link between KHSRP-bound snoRNAs and invasiveness and metastasis of pancreatic cancers. New therapies that prevent binding of KHSRP with specific snoRNAs may hold significant clinical promise.