Yan Xueli, Chang Jing, Sun Ruiying, Meng Xia, Wang Wei, Zeng Lizhong, Liu Boxuan, Li Wei, Yan Xuehua, Huang Chen, Zhao Yongxi, Li Zongfang, Yang Shuanying
Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
Department of Assisted Reproductive Centre, Northwest Women's and Children's Hospital Xi'an, Shaanxi, China.
Am J Transl Res. 2019 Aug 15;11(8):4881-4894. eCollection 2019.
DHX9 has numerous functions regulating transcription, translation, RNA processing and transport, and DNA replication and maintenance of genomic stability. It is involved in human cancers as either an oncogene or tumor suppressor. However, its role in the progression of lung cancer and underlying mechanisms remains unclear. In this study, we demonstrated that DHX9 is overexpressed in human lung cancer tissues and serum. Also, a favorable prognosis of lung adenocarcinoma is predicted when DHX9 is at a high level. DHX9 knockdown promoted cell proliferation, migration, and invasion and inhibited apoptosis progression in A549 cells. Moreover, DHX9 knockdown led to a significant decrease of E-cadherin expression, an increase of vimentin and snail, and a significant increase in the phosphorylation of STAT3 in A549 cells. In summary, our studies identified a novel role of DHX9 in driving tumor growth and epithelial-mesenchymal transition progress of A549 cells. We propose that the STAT3 pathway may be implicated in the DHX9-related epithelial-mesenchymal transition of lung adenocarcinoma. Therefore, DHX9 may be a prognostic marker or potential therapeutic target for lung adenocarcinoma.
DHX9具有多种调节转录、翻译、RNA加工与转运以及DNA复制和维持基因组稳定性的功能。它在人类癌症中作为癌基因或肿瘤抑制因子发挥作用。然而,其在肺癌进展中的作用及潜在机制仍不清楚。在本研究中,我们证明DHX9在人类肺癌组织和血清中过表达。此外,当DHX9处于高水平时,预测肺腺癌预后良好。敲低DHX9可促进A549细胞的增殖、迁移和侵袭,并抑制细胞凋亡进程。此外,敲低DHX9导致A549细胞中E-钙黏蛋白表达显著降低、波形蛋白和蜗牛蛋白增加,以及STAT3磷酸化显著增加。总之,我们的研究确定了DHX9在驱动A549细胞肿瘤生长和上皮-间质转化进程中的新作用。我们提出STAT3通路可能参与了肺腺癌中与DHX9相关的上皮-间质转化。因此,DHX9可能是肺腺癌的一个预后标志物或潜在治疗靶点。