Department of Oncology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China.
Department of Oncology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China.
Biochem Biophys Res Commun. 2018 Sep 26;504(1):164-170. doi: 10.1016/j.bbrc.2018.08.149. Epub 2018 Sep 1.
Accumulating evidence has identified microRNA-1179 (miR-1179) as a novel cancer-related miRNA that is dysregulated in multiple cancers and plays an important role in regulating cancer development and progression. However, little is known about the role of miR-1179 in non-small cell lung cancer (NSCLC). Thus, in the present study, we aimed to investigate the potential biological function and regulatory mechanism of miR-1179 in NSCLC. The results showed that decreased expression of miR-1179 expression was frequently detected in primary NSCLC tissues and cell lines. Overexpression of miR-1179 suppressed the growth and invasion of NSCLC cells in vitro while its inhibition promoted the opposite effect. Sperm-associated antigen 5 (SPAG5) was an identified as a target gene of miR-1179. Moreover, SPAG5 expression was increased in NSCLC cells and showed an inverse correlation with miR-1179 in NSCLC specimens. SPAG5 knockdown inhibited the growth and invasion of NSCLC cells, results that simulated a similar effect to miR-1179 overexpression. Mechanistic investigations showed that miR-1179 overexpression or SPAG5 knockdown significantly downregulated the activation of Akt signaling. Additionally, SPAG5 overexpression partially reversed the antitumor effect of miR-1179. Overall, our results demonstrated that miR-1179 inhibited the growth and invasion of NSCLC cells by targeting SPAG5 and inhibiting Akt, findings that highlight the importance of the miR-1179/SPAG5/Akt axis in the progression of NSCCL.
越来越多的证据表明，微小 RNA-1179（miR-1179）是一种新型的癌症相关 miRNA，在多种癌症中失调，在调节癌症发生和发展中发挥重要作用。然而，miR-1179 在非小细胞肺癌（NSCLC）中的作用知之甚少。因此，本研究旨在探讨 miR-1179 在 NSCLC 中的潜在生物学功能和调控机制。结果表明，miR-1179 的表达在原发性 NSCLC 组织和细胞系中经常下调。miR-1179 的过表达抑制了 NSCLC 细胞的体外生长和侵袭，而其抑制则促进了相反的效果。精子相关抗原 5（SPAG5）被鉴定为 miR-1179 的靶基因。此外，SPAG5 在 NSCLC 细胞中的表达增加，并与 NSCLC 标本中的 miR-1179 呈负相关。SPAG5 敲低抑制了 NSCLC 细胞的生长和侵袭，其结果类似于 miR-1179 的过表达。机制研究表明，miR-1179 过表达或 SPAG5 敲低显著下调 Akt 信号的激活。此外，SPAG5 的过表达部分逆转了 miR-1179 的抗肿瘤作用。总之，我们的研究结果表明，miR-1179 通过靶向 SPAG5 抑制 Akt 来抑制 NSCLC 细胞的生长和侵袭，强调了 miR-1179/SPAG5/Akt 轴在 NSCLC 进展中的重要性。
