MicroRNA-125b promotes tumor growth and suppresses apoptosis by targeting DRAM2 in retinoblastoma
MicroRNA-125b promotes tumor growth and suppresses apoptosis by targeting DRAM2 in retinoblastoma
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作者：
Bai, S.;Tian, B.;Li, F.
目的microRNAs（miRNAs）是一类非编码的小分子RNA，在多种生理和病理过程中起着重要的调节作用。然而，视网膜母细胞瘤（RB）中涉及miRNAs的调控机制在很大程度上仍然未知。miRNA miR-125 b在多种人类癌症中失调，例如乳腺癌、人肝细胞癌、卵巢癌和结肠直肠癌。然而，miR-125 b在RB中的意义尚未得到充分研究。方法采用实时荧光定量聚合酶链反应（real-time polymerase chain reaction，RT-PCR）检测人RB细胞系HXO-Rb 44、Y 79、SO-RB 50和正常人视网膜色素上皮细胞系ARPE-19中miR-125 b的表达水平，同时检测38对RB原发组织和癌旁组织中miR-125 b的表达。结果miR-125 b在RB细胞中表达显著上调，并与肿瘤细胞增殖和凋亡密切相关。此外，miR-125 b的过表达明显促进体外RB细胞增殖和迁移。体外功能获得实验进一步显示miR-125 b模拟物显著抑制RB细胞凋亡。结论miR-125 b是一种抑制RB细胞增殖和迁移的抑制基因，可通过下调抑制基因DRAM 2的表达促进RB细胞增殖和迁移，提示miR-125 b可能成为RB诊断和治疗的新靶点。
Purpose It is known that microRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms involving miRNAs in retinoblastoma (RB) remain largely unknown. The miRNA miR-125b is dysregulated in various human cancers such as breast cancer, human hepatocellular carcinoma, ovarian cancer, and colorectal cancer. However, the significance of miR-125b in RB has not been sufficiently investigated. Our objective was to explore the role of the miR-125b in RB.Methods In this study, we measured miR-125b levels using real-time polymerase chain reaction in human RB cell lines, including HXO-Rb44, Y79, SO-RB50, and the normal human retinal pigment epithelial cell line ARPE-19; a total of 38 pairs of primary RB tissues and adjacent noncancerous tissues were also measured. In addition, overexpression of miR-125b in RB cell lines was performed to determine the role of miR-125b in RB.Results We found that miR-125b is significantly upregulated in RB, and closely associated with tumor cell proliferation and apoptosis. In addition, overexpression of miR-125b apparently promotes RB cell proliferation and migration in vitro. Gain-of-function in vitro experiments further showed that the miR-125b mimic significantly suppressed RB cell apoptosis. A subsequent dual-luciferase reporter assay identified the suppressor gene DRAM2 as direct target of miR-125b.Conclusions Our data collectively demonstrate that miR-125b is a suppressor gene miRNA that can promote RB cell proliferation and migration by downregulating the suppressor gene DRAM2, indicating that miR-125b may represent a new potential diagnostic and therapeutic target for RB treatment.