Chan Lawrence W C, Wang Fengfeng, Meng Fei, Wang Lili, Wong Sze Chuen Cesar, Au Joseph S K, Yang Sijun, Cho William C S
Department of Health Technology and Informatics, Hong Kong Polytechnic University Hong Kong, Hong Kong.
Hong Kong Adventist Hospital Hong Kong, Hong Kong.
Front Genet. 2017 Feb 2;8:8. doi: 10.3389/fgene.2017.00008. eCollection 2017.
Non-small cell lung cancer (NSCLC) comprises about 84% of all lung cancers. Many treatment options are available but the survival rate is still very low due to drug resistance. It has been found that phosphoinositide-3-kinase (PI3K) affects sensitivity to tyrosine kinase inhibitors (TKIs), including gefitinib and erlotinib. Expression level of seven in absentia homolog 2 (SIAH2), an E3 ubiquitin-protein ligase, is upregulated in NSCLC and correlated with tumor grade. However, the relationship between PI3K and SIAH2 remains unclear and therefore it is not known whether they can act as treatment co-targets and theranostic dual markers for overcoming TKI resistance. It is worthy to note that PI3K and SIAH2 are potentially regulated by a common group of microRNAs in miR-30 family. Our bioinformatics analyses showed upregulated SIAH2 expression in NSCLC based on mass spectrometry data, explored its indirect interaction with PI3K and predicted their targeting microRNAs in common. We have also explored the potential role of miR-30 family in the modulation of PI3K-SIAH2 interaction in NSCLC.
非小细胞肺癌（NSCLC）约占所有肺癌的84%。虽然有多种治疗选择，但由于耐药性，生存率仍然很低。研究发现，磷脂酰肌醇-3-激酶（PI3K）会影响对酪氨酸激酶抑制剂（TKI）的敏感性，包括吉非替尼和厄洛替尼。E3泛素蛋白连接酶七缺席同源物2（SIAH2）的表达水平在NSCLC中上调，且与肿瘤分级相关。然而，PI3K与SIAH2之间的关系仍不清楚，因此尚不清楚它们是否可作为克服TKI耐药性的联合治疗靶点和诊疗双重标志物。值得注意的是，PI3K和SIAH2可能受miR-30家族一组共同的微小RNA调控。我们的生物信息学分析基于质谱数据显示NSCLC中SIAH2表达上调，探究了其与PI3K的间接相互作用，并预测了它们共同的靶向微小RNA。我们还探讨了miR-30家族在调节NSCLC中PI3K-SIAH2相互作用方面的潜在作用。
