Xu Yanjun, Jin Juan, Xu Jiawei, Shao Yang W, Fan Yun
1 Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, China.
2 Department of Cell Biology and Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, China.
Tumour Biol. 2017 Jun;39(6):1010428317711140. doi: 10.1177/1010428317711140.
Lung cancer ranks as the first most common cancer and the first leading cause of cancer-related death in China and worldwide. Due to the difficulty in early diagnosis and the onset of cancer metastasis, the 5-year survival rate of lung cancer remains low. JAK2 has emerged as pivotal participant in biological processes, often dysregulated in a range of cancers. Recently our study found that JAK2 might play an important role in lung cancer pathogenesis. While our understanding of JAK2 in the onset and progression of lung cancer is still in its infancy, there is no doubt that understanding the variations and functions of JAK2 will certainly secure strong biomarkers and improve treatment options for lung cancer patients. The expression level of JAK2 mRNA was assayed using RT-PCR. JAK2 mutations and amplification were detected using next-generation sequencing (NGS). The shRNA and overexpression plasmids of JAK2 were conducted. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazoliumbromide) assay, Trans-well migration and Matrigel invasion assay were conducted to study the proliferation, migration and invasion abilities of lung adenocarcinoma cells independently. We found that JAK2 mRNA was up-regulated in lung adenocarcinoma tissues when compared with their adjacent non-tumor tissues, and was associated with lymph node metastasis ( p < 0.05). JAK2 V617F and N30S mutations and JAK2 amplification were detected by NGS in plasmid samples in patients with lung adenocarcinoma. Downregulation of JAK2 inhibited the proliferation, migration and invasion abilities of lung adenocarcinoma A549 cells. Moreover, overexpression of JAK2 induced the proliferation, migration and invasion abilities of A549 cells. Thus, the up-regulation, mutation and amplification of JAK2 detected in lung adenocarcinoma may participate in lung cancer progression by regulating cancer cells' proliferation, migration and invasion.
肺癌是中国和全球最常见的癌症，也是癌症相关死亡的首要原因。由于早期诊断困难以及癌症转移的发生，肺癌的5年生存率仍然很低。JAK2已成为生物过程中的关键参与者，在一系列癌症中常常失调。最近我们的研究发现，JAK2可能在肺癌发病机制中起重要作用。虽然我们对JAK2在肺癌发生和发展中的理解仍处于起步阶段，但毫无疑问，了解JAK2的变异和功能肯定会获得强大的生物标志物，并改善肺癌患者的治疗选择。使用RT-PCR检测JAK2 mRNA的表达水平。使用下一代测序（NGS）检测JAK2突变和扩增。构建了JAK2的shRNA和过表达质粒。分别进行MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）法、Trans-well迁移实验和基质胶侵袭实验，以研究肺腺癌细胞的增殖、迁移和侵袭能力。我们发现，与相邻的非肿瘤组织相比，肺腺癌组织中JAK2 mRNA上调，且与淋巴结转移相关（p<0.05）。通过NGS在肺腺癌患者的质粒样本中检测到JAK2 V617F和N30S突变以及JAK2扩增。JAK2的下调抑制了肺腺癌A549细胞的增殖、迁移和侵袭能力。此外，JAK2的过表达诱导了A549细胞的增殖、迁移和侵袭能力。因此，在肺腺癌中检测到的JAK2上调、突变和扩增可能通过调节癌细胞的增殖、迁移和侵袭参与肺癌进展。
