Lv Yan, Yang Huijun, Ma Xingkai, Wu Geping
1Center of Translational Medicine, The Affiliated Zhangjiagang Hospital of Soochow University, No. 68, Jiyang West Road, Suzhou, China.
2Department of Otolaryngology, The Affiliated Zhangjiagang Hospital of Soochow University, No. 68, Jiyang West Road, Suzhou, China.
Cancer Cell Int. 2019 Jul 19;19:187. doi: 10.1186/s12935-019-0915-x. eCollection 2019.
MicroRNAs (miRNAs) play crucial roles in varieties of cancers, particularly in tumorigenesis, progression, and migration. Dysregulation of miR-28 was reported to occur in various types of human malignancies. In humans, two different mature miRNA sequences are excised from opposite arms of the stem-loop pre-miR-28, hsa-miR-28-3p and hsamiR-28-5p. However, the expression and distinct role of miR-28-3p and miR-28-5p in nasopharyngeal carcinoma (NPC) remain undetermined.
The expressions of miR-28-3p/-5p in human NPC tissues were tested by quantitative real-time PCR. miR-28-3p/-5p were overexpressed by mimics and silenced by inhibitors. The roles of miR-28-3p/-5p in NPC development were studied using cultured HONE-1 cells.
The mRNA expression levels of miR-28-3p and -5p were significantly decreased in NPC tissues in comparison with adjacent normal tissues. Overexpression of miR-28-5p suppressed NPC cell proliferation and induced cell cycle arrest and apoptosis, while miR-28-3p promoted NPC cell migration and invasion. The miRNAs effected on different signal pathways: miR-28-5p altered expression of cyclin D1 and influenced the PI3K/AKT signaling pathway. In contrast, miR-28-3p downregulated Nm23-H1 and accelerated the process of EMT.
miR-28-3p and -5p were both downregulated in NPC tissues but had distinct biological effects in NPC cells. They may serve as potential prognostic markers and therapeutic targets for NPC.
微小RNA(miRNA)在多种癌症中发挥关键作用,尤其是在肿瘤发生、进展和迁移过程中。据报道,miR - 28的失调发生在各种类型的人类恶性肿瘤中。在人类中,从茎环前体miR - 28的相反臂上切除两个不同的成熟miRNA序列,即hsa - miR - 28 - 3p和hsa - miR - 28 - 5p。然而,miR - 28 - 3p和miR - 28 - 5p在鼻咽癌(NPC)中的表达及不同作用仍未明确。
通过定量实时PCR检测人NPC组织中miR - 28 - 3p/-5p的表达。用模拟物使miR - 28 - 3p/-5p过表达,用抑制剂使其沉默。使用培养的HONE - 1细胞研究miR - 28 - 3p/-5p在NPC发展中的作用。
与相邻正常组织相比,NPC组织中miR - 28 - 3p和 - 5p的mRNA表达水平显著降低。miR - 28 - 5p的过表达抑制NPC细胞增殖并诱导细胞周期停滞和凋亡,而miR - 28 - 3p促进NPC细胞迁移和侵袭。这些miRNA影响不同的信号通路:miR - 28 - 5p改变细胞周期蛋白D1的表达并影响PI3K/AKT信号通路。相反,miR - 28 - 3p下调Nm23 - H1并加速EMT进程。
miR - 28 - 3p和 - 5p在NPC组织中均下调,但在NPC细胞中具有不同的生物学效应。它们可能作为NPC潜在的预后标志物和治疗靶点。