Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Biochem Biophys Res Commun. 2014 Feb 28;445(1):196-202. doi: 10.1016/j.bbrc.2014.01.175. Epub 2014 Feb 4.
SET and hnRNPK are proteins involved in gene expression and regulation of cellular signaling. We previously demonstrated that SET accumulates in head and neck squamous cell carcinoma (HNSCC); hnRNPK is a prognostic marker in cancer. Here, we postulate that SET and hnRNPK proteins interact to promote tumorigenesis. We performed studies in HEK293 and HNSCC (HN6, HN12, and HN13) cell lines with SET/hnRNPK overexpression and knockdown, respectively. We found that SET and/or hnRNPK protein accumulation increased cellular proliferation. SET accumulation up-regulated hnRNPK mRNA and total/phosphorylated protein, promoted hnRNPK nuclear location, and reduced Bcl-x mRNA levels. SET protein directly interacted with hnRNPK, increasing both its binding to nucleic acids and Bcl-xS repression. We propose that hnRNPK should be a new target of SET and that SET-hnRNPK interaction, in turn, has potential implications in cell survival and malignant transformation.
SET 和 hnRNPK 是参与基因表达和细胞信号转导调节的蛋白质。我们之前的研究表明，SET 在头颈部鳞状细胞癌（HNSCC）中积累；hnRNPK 是癌症的预后标志物。在这里，我们假设 SET 和 hnRNPK 蛋白相互作用以促进肿瘤发生。我们分别在过表达和敲低 SET/hnRNPK 的 HEK293 和 HNSCC（HN6、HN12 和 HN13）细胞系中进行了研究。我们发现 SET 和/或 hnRNPK 蛋白积累增加了细胞增殖。SET 积累上调了 hnRNPK mRNA 和总/磷酸化蛋白，促进了 hnRNPK 的核定位，并降低了 Bcl-x mRNA 水平。SET 蛋白与 hnRNPK 直接相互作用，增加了其与核酸的结合和 Bcl-xS 抑制。我们提出 hnRNPK 应该是 SET 的一个新靶标，SET-hnRNPK 相互作用反过来又可能对细胞存活和恶性转化有影响。
