Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin, China.
J Cell Biochem. 2018 Aug;119(8):6461-6469. doi: 10.1002/jcb.26671. Epub 2018 May 9.
Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence, and high degree of metastasis. This study aimed to investigate the effects of long noncoding RNA antisense ncRNA in the abundant in neuroepithelium area (ANA)/B-cell translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human osteosarcoma cells were evaluated using qRT-PCR. Effects of ASBEL knockdown on cell viability, migration, and invasion were detected using trypan blue exclusion assay, cell migration, and cell invasion assay, respectively. The regulatory effects of ASBEL on microRNA-21 (miR-21) were analyzed using qRT-PCR. The roles of miR-21 and protein phosphatase 2A (PP2A), the possible downstream factor of miR-21, in osteosarcoma cell proliferation, migration, and invasion were also explored. The results showed that ASBEL was highly expressed in osteosarcoma cells. Knockdown of ASBEL inhibited osteosarcoma cell viability, migration, and invasion, as well as the expression level of miR-21. PP2A was a direct target of miR-21, which participated in the effects of ASBEL and miR-21 on the activation of phosphatidylinositol 3-kinase/protein kinase 3/glycogen synthase kinase-3β (PI3K/AKT/GSK3β) and mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion. In conclusion, we verified that ASBEL-miR-21-PP2A pathway might play critical regulatory effects on the pathogenesis of osteosarcoma and could be as the potential therapeutic target and biomarker for osteosarcoma treatment.
骨肉瘤是儿童和青少年中最常见的恶性骨肿瘤，具有发病率高、复发率高、转移率高的特点。本研究旨在探讨富含神经上皮区域的长链非编码 RNA 反义 ncRNA/ B 细胞易位基因 3（lncRNA ASBEL）对骨肉瘤发病机制的影响。采用 qRT-PCR 检测 ASBEL 在人成骨细胞和人骨肉瘤细胞中的表达水平。采用台盼蓝排除试验、细胞迁移和细胞侵袭试验分别检测 ASBEL 敲低对细胞活力、迁移和侵袭的影响。采用 qRT-PCR 分析 ASBEL 对 microRNA-21（miR-21）的调控作用。还探讨了 miR-21 和蛋白磷酸酶 2A（PP2A），miR-21 的可能下游因子，在骨肉瘤细胞增殖、迁移和侵袭中的作用。结果表明，ASBEL 在骨肉瘤细胞中高表达。ASBEL 敲低抑制骨肉瘤细胞活力、迁移和侵袭，以及 miR-21 的表达水平。PP2A 是 miR-21 的直接靶标，参与 ASBEL 和 miR-21 对磷脂酰肌醇 3-激酶/蛋白激酶 3/糖原合成酶激酶-3β（PI3K/AKT/GSK3β）和丝裂原激活蛋白激酶/细胞外调节蛋白激酶（MEK/ERK）信号通路的激活以及增强骨肉瘤细胞增殖、迁移和侵袭的作用。综上所述，我们验证了 ASBEL-miR-21-PP2A 通路可能对骨肉瘤的发病机制具有重要的调节作用，可作为骨肉瘤治疗的潜在治疗靶点和生物标志物。
