Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
Center of Kidney Disease, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Jul 10;51(7):677-687. doi: 10.1093/abbs/gmz053.
Lung cancer is the leading cause of cancer death worldwide, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of diagnostic cases. The molecular mechanisms of NSCLC pathogenesis are not well understood. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein that regulates gene expression and signal transduction and closely associated with tumorigenesis, but its mechanism of action in the pathogenesis of NSCLC is unclear. In this study, we observed that the expression pattern of hnRNPK in H1299 lung adenocarcinoma cells varied depending on the cell density in culture. Moreover, hnRNPK stimulated the ability of proliferation and colony formation of H1299 cells, which is important for the multilayered cell growth in culture. We further investigated whether there is an association between hnRNPK and the elements involved in the cell contact inhibition pathway. By using quantitative reverse transcriptase-polymerase chain reaction assay and a YAP activity reporter system, we found that hnRNPK upregulated the mRNA and protein levels and transcriptional activity of Yes-associated protein 1 (YAP), a master negative regulator of Hippo contact inhibition pathway. Furthermore, YAP knockdown with siRNA abolished the stimulatory effect of hnRNPK on H1299 cell proliferation. These results suggested that YAP could be one of the effectors of hnRNPK. Our data may provide new clues for further understanding the biological functions of hnRNPK, particularly in the context of lung adenocarcinoma oncogenesis.
肺癌是全球癌症死亡的主要原因，非小细胞肺癌（NSCLC）占诊断病例的 80%-85%。NSCLC 发病机制的分子机制尚未完全了解。异质核核糖核蛋白 K（hnRNPK）是一种多功能蛋白，可调节基因表达和信号转导，与肿瘤发生密切相关，但它在 NSCLC 发病机制中的作用机制尚不清楚。在这项研究中，我们观察到 hnRNPK 在 H1299 肺腺癌细胞中的表达模式随培养细胞密度而异。此外，hnRNPK 刺激 H1299 细胞的增殖和集落形成能力，这对于培养中的多层细胞生长很重要。我们进一步研究了 hnRNPK 是否与细胞接触抑制途径中涉及的元素有关。通过使用定量逆转录-聚合酶链反应（qRT-PCR） assay 和 YAP 活性报告系统，我们发现 hnRNPK 上调了 Yes 相关蛋白 1（YAP）的 mRNA 和蛋白水平及其转录活性，YAP 是 Hippo 接触抑制途径的主要负调控因子。此外，用 siRNA 敲低 YAP 可消除 hnRNPK 对 H1299 细胞增殖的刺激作用。这些结果表明 YAP 可能是 hnRNPK 的效应物之一。我们的数据可能为进一步了解 hnRNPK 的生物学功能提供新的线索，特别是在肺腺癌致癌作用方面。
