Abstract Objective To investigate the value of serum miR-17-92 cluster in the diagnosis of retinoblastoma (RB). Methods Serum samples were collected from 20 children with RB and 20 healthy controls. Quantitative real-time PCR was used to measure the expression of miR-17-92 cluster. The expression of miR-17-92 cluster was compared between children with different stages of RB and the changes in the expression of miR-17-92 cluster after multimodality therapy were analyzed. The receiver operating characteristic (ROC) curve was used to investigate the value of serum miR-17-92 cluster in the diagnosis of RB. Results Compared with the healthy controls, the children with RB had signifcantly higher relative expression of miR-17-3P, miR-17-5P, miR-18a, and miR-20a in serum (P < 0.05), and miR-18a showed the greatest increase. There were no signifcant differences in the relative expression of miR-19a, miR-19b-1, and miR-92a-1 between children with RB and healthy controls (P > 0.05). There were no signifcant differences in the expression of miR-17-5P, miR-17-3P, miR-18a, and miR-20a between the children with early-to-moderate stage of RB and those with advanced stage of RB (P > 0.05), but there were signifcant reductions after multimodality therapy (P < 0.05). In the diagnosis of RB, the areas under the ROC curve (AUCs) for serum miR-17-3P, miR-17-5P, miR-18a, and miR-20a were 0.770, 0.755, 0.828, and 0.665 respectively, and miR-18a had the largest AUC, with a sensitivity of 90% and a specifcity of 65%. Conclusions miR-17-3P, miR-17-5P, miR-18a, and miR-20a are highly expressed in the serum of children with RB, and miR-18a may be used as a new marker for the diagnosis of RB.
Chang CY, Chiou TJ, Hwang B, et al. Retinoblastoma in Taiwan:survival rate and prognostic factors[J]. Jpn J Ophthalmol, 2006, 50(3):242-249.
[3]
Attar M, Arefian E, Nabiuni M, et al. MicroRNA 17-92 expressed by a transposone-based vector changes expression level of cell-cycle-related genes[J]. Cell Biol Int, 2012, 36(11):1005-1012.
[4]
Lillington DM, Kingston JE, Coen PG, et al. Comparative genomic hybridization of 49 primary retinoblastoma tumors identifes chromosomal regions associated with histopathology, progression, and patient outcome[J]. Genes Chromosomes Cancer, 2003, 36(2):121-128.
[5]
Kandalam MM, Beta M, Maheswari UK, et al. Oncogenic microRNA 17-92 cluster is regulated by epithelial cell adhesion molecule and could be a potential therapeutic target in retinoblastoma[J]. Mol Vis, 2012, 18:2279-2287.
Andreas E, Hoelker M, Neuhoff C, et al. MicroRNA 17-92 cluster regulates proliferation and differentiation of bovine granulosa cells by targeting PTEN and BMPR2 genes[J]. Cell Tissue Res, 2016, 366(1):219-230.
[14]
Dellago H, Bobbili MR, Grillari J. MicroRNA-17-5p:At the crossroads of cancer and aging-A mini-review[J]. Gerontology, 2017, 63(1):20-28.
[15]
Brockway S, Zeleznik-Le NJ. WEE1 is a validated target of the microRNA miR-17-92 cluster in leukemia[J]. Cancer Genet, 2015, 208(5):279-287.
Conkrite K, Sundby M, Mukai S, et al. miR-17~92 cooperates with RB pathway mutations to promote retinoblastoma[J]. Genes Dev, 2011, 25(16):1734-1745.
[18]
Nittner D, Lambertz I, Clermont F, et al. Synthetic lethality between Rb, p53 and Dicer or miR-17-92 in retinal progenitors suppresses retinoblastoma formation[J]. Nat Cell Biol, 2012, 14(9):958-965.
[19]
Yang Y, Mei Q. miRNA signature identification of retinoblastoma and the correlations between differentially expressed miRNAs during retinoblastoma progression[J]. Mol Vis, 2015, 21:1307-1317.
[20]
Fadakar P, Akbari A, Ghassemi F, et al. Evaluation of SD-208, a TGF-β-RI kinase inhibitor, as an anticancer agent in retinoblastoma[J]. Acta Med Iran, 2016, 54(6):352-358.
[21]
Jo DH, Kim JH, Cho CS, et al. STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters[J]. Oncotarget, 2014, 5(22):11513-11525.