SRPK1 facilitates tumor cell growth via modulating the small nucleolar RNA expression in gastric cancer
SRPK1 facilitates tumor cell growth via modulating the small nucleolar RNA expression in gastric cancer
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SRPK1 通过调节胃癌中小核仁 RNA 的表达来促进肿瘤细胞生长。
DOI：
10.1002/jcp.28036
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发表时间：
2019-08-01
影响因子：
5.6
通讯作者：
Gao, Yong
中科院分区：
文献类型：
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作者：
Li, Yandong;Yu, Shijun;Gao, Yong
丝氨酸-精氨酸蛋白激酶1（SRPK 1）是选择性剪接的主要调节因子，通过磷酸化富含丝氨酸/精氨酸重复序列的剪接因子。它的过度表达已在多种癌症类型中发现，并有助于癌症的发展。本文报道SRPK 1在胃癌细胞生长中的作用及其机制。通过免疫组化和Western blot分析，我们发现SRPK 1在胃癌组织中的表达与其邻近的正常组织相比频繁上调。在细胞活力测定、集落形成测定和裸鼠异种移植模型中，GC细胞中SRPK 1的敲低抑制细胞生长，而SRPK 1的过表达在这些测定中促进相反的表型。通过互补DNA微阵列分析，我们发现SRPK 1基因敲低对大多数核仁小RNA的表达有显著的抑制作用。其中，选择snoRA 42、snoRA 74 A和snoRD 10用于进一步的功能实验。在平板和软琼脂中的细胞生长曲线表明，这三种snoRNA在GC中具有潜在的致癌功能。此外，SRPK 1可以与NCL，一个参与核糖体合成和成熟的核仁磷蛋白免疫共沉淀。这些结果表明SRPK 1通过snoRNA介导的信号转导新的可能机制促进GC的发展。
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.