Huang Gang, Pan Jiongwei, Ye Zaiting, Fang Bingmu, Cheng Wei, Cao Zhuo
Department of Traditional Chinese Medicine, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, 323000, China.
Department of Respiratory, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui, 323000, China.
Oncotarget. 2017 Oct 27;8(61):104206-104215. doi: 10.18632/oncotarget.22171. eCollection 2017 Nov 28.
Platinum-based chemotherapy is still be the standard treatment for non-small cell lung cancer (NSCLC). Recently, studies demonstrate that some kinds of microRNAs (miRNAs) are associated with chemosensitivity of NSCLC cells to platinum-based treatment. Unfortunately, cancer cells usually change their expression profile of miRNAs to form drug resistance against chemotherapy. In the present study, we focused on miR-216b to investigate whether miR-216b determined sensitivity of NSCLC cells to cisplatin. We observed that expression level of miR-216b was significantly decreased in NSCLC cell lines when they were under the cisplatin treatment. However, restore of miR-216b by transfecting with its mimics was found to increase the cytotoxicity of cisplatin to NSCLC cells. Studies on mechanisms elucidated that miR-216b targeted c-Jun in NSCLC. Overexpression of miR-216b can suppress the cisplatin-induced upregulation of c-Jun. As the downstream, overexpression of Bcl-xl induced by c-Jun/ATF2 heterodimers was inhibited in miR-216b transfected NSCLC cells. Since Bcl-xl is a key anti-apoptotic protein, we found that sensitivity of NSCLC cells to cisplatin-induced apoptosis was significantly increased because of the overexpression of miR-216b.
铂类化疗仍然是治疗非小细胞肺癌（NSCLC）的标准方法。最近，研究表明某些种类的微小RNA（miRNA）与NSCLC细胞对铂类治疗的化疗敏感性相关。不幸的是，癌细胞通常会改变其miRNA的表达谱以形成对化疗的耐药性。在本研究中，我们聚焦于miR-216b来探究其是否决定NSCLC细胞对顺铂的敏感性。我们观察到，当NSCLC细胞系接受顺铂处理时，miR-216b的表达水平显著降低。然而，通过转染其模拟物来恢复miR-216b的表达，发现可增加顺铂对NSCLC细胞的细胞毒性。对机制的研究阐明，在NSCLC中miR-216b靶向c-Jun。miR-216b的过表达可抑制顺铂诱导的c-Jun上调。作为下游效应，在转染了miR-216b的NSCLC细胞中，由c-Jun/ATF2异二聚体诱导的Bcl-xl过表达受到抑制。由于Bcl-xl是一种关键的抗凋亡蛋白，我们发现miR-216b的过表达显著增加了NSCLC细胞对顺铂诱导凋亡的敏感性。
