Department of Gastroenterology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China.
Department of General Surgery, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154003, P.R. China.
Mol Med Rep. 2019 Jan;19(1):719-726. doi: 10.3892/mmr.2018.9651. Epub 2018 Nov 13.
Multiple previous studies have demonstrated that the dysregulation of microRNAs (miRNAs) is implicated in the occurrence and development of pancreatic cancer. Therefore, a further characterisation of deregulated miRNAs in pancreatic cancer may provide novel insight into the oncogenesis and progression of pancreatic cancer, which may facilitate the identification of effective therapeutic targets for treating patients with this disease. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis demonstrated that the expression level of miRNA‑584‑5p (miR‑584) was significantly decreased in pancreatic cancer tissues and cell lines. It was demonstrated that restoration of miR‑584 expression significantly suppressed the proliferative and invasive ability of pancreatic cancer cells. Bioinformatics analysis predicted that cyclin D1 (CCND1) was a putative target of miR‑584. Subsequent experiments demonstrated that CCND1 was a direct target gene of miR‑584 in pancreatic cancer cells. Furthermore, the inhibition of CCND1 mimicked the suppressive effect of miR‑584 overexpression in pancreatic cancer cells. The restoration of CCND1 expression significantly abolished the inhibitory effects of miR‑584 overexpression on pancreatic cancer cells. Collectively, the present results demonstrated that miR‑584 inhibited the development of pancreatic cancer by directly targeting CCND1, suggesting that this miRNA may represent a potential therapeutic target for this fatal disease.
先前的多项研究表明,microRNAs(miRNAs)的失调与胰腺癌的发生和发展有关。因此,对胰腺癌中失调的 miRNAs 进行进一步的表征可能为胰腺癌的发生和发展提供新的见解,这可能有助于确定治疗这种疾病患者的有效治疗靶点。在本研究中,逆转录-定量聚合酶链反应分析表明,miRNA-584-5p(miR-584)在胰腺癌组织和细胞系中的表达水平显著降低。研究表明,恢复 miR-584 的表达显著抑制了胰腺癌细胞的增殖和侵袭能力。生物信息学分析预测细胞周期蛋白 D1(CCND1)是 miR-584 的一个潜在靶基因。随后的实验表明,CCND1 是胰腺癌细胞中 miR-584 的直接靶基因。此外,抑制 CCND1 模拟了 miR-584 过表达对胰腺癌细胞的抑制作用。恢复 CCND1 的表达显著消除了 miR-584 过表达对胰腺癌细胞的抑制作用。综上所述,本研究结果表明,miR-584 通过直接靶向 CCND1 抑制胰腺癌的发展,提示该 miRNA 可能成为这种致命疾病的潜在治疗靶点。