SRPK1 facilitates tumor cell growth via modulating the small nucleolar RNA expression in gastric cancer

J Cell Physiol. 2019 Aug;234(8):13582-13591. doi: 10.1002/jcp.28036. Epub 2019 Jan 11.

Abstract

Serine-arginine protein kinase 1 (SRPK1) is the main regulator in alternative splicing by phosphorylating splicing factors rich in serine/arginine repeats. Its overexpression has been found in multiple cancer types and contributes to cancer development. Here we report the role of SRPK1 and underlying mechanism in gastric cancer (GC) cell growth. We found that SRPK1 was frequently upregulated in GC samples compared with their adjacent corresponding normal tissues by immunohistochemistry and western blot analysis. Knockdown of SRPK1 in GC cells suppressed cell growth in cell viability assays, colony formation assays and nude mice xenograft model, whereas overexpression of SRPK1 promotes opposite phenotypes in these assays. By a complementary DNA microarray analysis, we found that SRPK1 knockdown had significant inhibitory effects on a majority of small nucleolar RNAs expression. Among them, snoRA42, snoRA74A, and snoRD10 were selected for further functional experiments. Cell growth curves on a plate and in soft agar indicated that the three snoRNAs play potential oncogenic function in GC. In addition, SRPK1 could co-immunoprecipitated with NCL, a nucleolar phosphoprotein involved in the synthesis and maturation of ribosomes. These results suggested that SRPK1 contributes to GC development by a new possible mechanism involving snoRNAs mediated signaling.

Keywords: SRPK1; gastric cancer; snoRNAs; tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / physiology
  • Gene Expression Regulation, Neoplastic / physiology*
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA, Small Nucleolar / biosynthesis*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*

Substances

  • RNA, Small Nucleolar
  • SRPK1 protein, human
  • Protein Serine-Threonine Kinases