KHSRP-bound small nucleolar RNAs associate with promotion of cell invasiveness and metastasis of pancreatic cancer.
KHSRP-bound small nucleolar RNAs associate with promotion of cell invasiveness and metastasis of pancreatic cancer.
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DOI：
10.18632/oncotarget.27413
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发表时间：
2020-01-14
期刊：
影响因子：
--
通讯作者：
Ogasawara, Mitsunari
中科院分区：
文献类型：
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作者：
Taniuchi, Keisuke;Ogasawara, Mitsunari
KH型剪接调节蛋白（KH-type splicing regulatory protein，KHSRP）是一种RNA结合蛋白，参与多种细胞过程，包括细胞核内的剪接和细胞质内mRNA的定位和降解。本研究报告KHSRP促进胰腺癌细胞的侵袭和转移。KHSRP定位于胰腺癌细胞系的细胞核和细胞突起。小分子干扰RNA抑制KHSRP可减少胰腺癌细胞突起的数量，抑制胰腺癌细胞的侵袭和转移。KHSRP定位于胰腺癌细胞的细胞质RNA颗粒中，RNA免疫沉淀-测序分析显示，与KHSRP免疫沉淀的富集RNA大多数是小核仁RNA（snoRNA）。特异性KHSRP结合的snoRNA，SNORA 18和SNORA 22，与细胞突起的形成相关。因此，SNORA 18和SNORA 22有助于细胞侵袭和肿瘤转移。我们的研究结果提供了深入了解KHSRP结合的snoRNA和胰腺癌的侵袭性和转移之间的联系。阻止KHSRP与特异性snoRNA结合的新疗法可能具有重要的临床前景。
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.