Department of Geriatrics, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, P.R. China.
Mol Med Rep. 2016 Oct;14(4):3021-8. doi: 10.3892/mmr.2016.5643. Epub 2016 Aug 19.
MicroRNAs (miRNAs) have been demonstrated to be critical in regulating tumor development and progression. The present study investigated the expression of miR‑588 using reverse transcription‑quantitative polymerase chain reaction analysis in 85 cases of lung squamous cell carcinoma (SCC), and observed the correlation between the expression of miR‑588 with clinical pathologic features. The results indicated that the expression of miR‑588 was predominantly lower in the tumor samples, compared with non‑tumorous samples, and was negatively associated with tumor stages and lymph node invasion. The present study also examined the significance of the expression of miR‑588 in SCC using gain‑ and loss‑of‑function analyses. It was found that miR‑588 inhibited tumor cell migration and invasion. In addition, it was revealed that the overexpression of miR‑588 in SCC cells reduced the mRNA and protein levels of progranulin (GRN), whereas miR‑588 silencing increased the expression of GRN. A luciferase activity assay showed that miR‑588 was able to directly bind to the 3'untranslated region of GRN and regulate its expression. Furthermore, it was found that the expression of GRN was inversely correlated with the expression of miR‑588 in 85 paired SCC samples. These results indicated that GRN was involved in the miR-588-mediated suppressive functions in the progression of SCC.
微小 RNA（miRNAs）已被证明在调节肿瘤的发生和发展中起着关键作用。本研究采用逆转录定量聚合酶链反应分析，检测了 85 例肺鳞癌（SCC）中 miR-588 的表达，并观察了 miR-588 的表达与临床病理特征之间的相关性。结果表明，miR-588 在肿瘤组织中的表达明显低于非肿瘤组织，且与肿瘤分期和淋巴结浸润呈负相关。本研究还通过增益和缺失功能分析，探讨了 miR-588 在 SCC 中的表达意义。结果表明，miR-588 抑制肿瘤细胞的迁移和侵袭。此外，还揭示了在 SCC 细胞中过表达 miR-588 可降低颗粒蛋白前体（GRN）的 mRNA 和蛋白水平，而 miR-588 沉默则增加了 GRN 的表达。荧光素酶活性测定表明，miR-588 可直接与 GRN 的 3'非翻译区结合，从而调节其表达。此外，还发现 85 对 SCC 样本中 GRN 的表达与 miR-588 的表达呈负相关。这些结果表明，GRN 参与了 miR-588 在 SCC 进展中介导的抑制功能。
