Li Hailing, Li Jilin, Shi Baolin, Chen Feng
Department of Endocrinology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China.
Department of Medical Laboratory Medicine, Family Planning Guidance Center of Weifang, Weifang, Shandong 261061, P.R. China.
Mol Med Rep. 2017 Jul;16(1):466-472. doi: 10.3892/mmr.2017.6602. Epub 2017 May 18.
Although microRNA-296 (miR-296) has been studied in various types of human cancer, its expression, biological role and mechanism of action in pancreatic cancer remains to be elucidated. The aim of the current study was to investigate the expression level, possible roles and underlying molecular mechanisms of miR‑296 in pancreatic cancer. The present study revealed that miR‑296 is significantly downregulated in tissue from patients with pancreatic cancer and in human pancreatic carcinoma cell lines, when compared with matched healthy tissue and normal human pancreatic cell lines, respectively. In addition, restoration of miR‑296 expression was revealed to inhibit the proliferation, migration and invasive activity of pancreatic cancer cells. Furthermore, bioinformatics analysis and a luciferase reporter assay validated the AKT2 gene as a direct target of miR‑296 in pancreatic cancer. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis revealed that miR‑296 was able to decrease AKT2 expression at the post‑transcriptional level. Notably, the effects of AKT2 knockdown were similar to miR‑296 overexpression in pancreatic cancer. In conclusion, the present findings indicate a role for miR‑296 as a tumor suppressor in pancreatic cancer through directly targeting AKT2, thus suggesting that miR‑296 may serve as a potential therapeutic target for the treatment of pancreatic cancer.
尽管微小RNA-296（miR-296）已在多种类型的人类癌症中得到研究，但其在胰腺癌中的表达、生物学作用及作用机制仍有待阐明。本研究的目的是探讨miR-296在胰腺癌中的表达水平、可能的作用及潜在分子机制。本研究显示，与匹配的健康组织和正常人类胰腺细胞系相比，miR-296在胰腺癌患者的组织及人类胰腺癌细胞系中显著下调。此外，恢复miR-296表达可抑制胰腺癌细胞的增殖、迁移及侵袭活性。此外，生物信息学分析和荧光素酶报告基因检测证实AKT2基因是miR-296在胰腺癌中的直接靶点。逆转录-定量聚合酶链反应和蛋白质印迹分析显示，miR-296能够在转录后水平降低AKT2的表达。值得注意的是，敲低AKT2的效果与miR-296在胰腺癌中过表达的效果相似。总之，本研究结果表明miR-296通过直接靶向AKT2在胰腺癌中发挥肿瘤抑制作用，因此提示miR-296可能成为治疗胰腺癌的潜在治疗靶点。
