Department of Inpatient Area 1 of Pediatric Surgery, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Eur Rev Med Pharmacol Sci. 2018 Aug;22(16):5156-5164. doi: 10.26355/eurrev_201808_15711.
Osteosarcoma is a malignant bone tumor with high incidence. The prognosis of osteosarcoma is very poor when it is diagnosed with metastasis. Numerous studies have demonstrated that aberrant expressions of microRNAs are involved in cancer initiation and development. However, the potential role of miR-214 in osteosarcoma remains largely unrevealed. The current study investigated the relationship between the miR-214 and TNF receptor-associated factor 3 (TRAF3) in osteosarcoma tissues and cell lines. We also aimed to evaluate the potential roles of miR-214 on the occurrence and metastasis in osteosarcoma and verify its effect on the regulation of TRAF3.
The miR-214 expression and TRAF3 expression in osteosarcoma tissue samples and cell line were measured using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Followed by transfection assays, transwell assay was conducted to detect the migration and invasion abilities of osteosarcoma cells. Subsequently, Western blotting and luciferase reporter assay were performed in osteosarcoma cells to confirm the target of miR-214.
The results showed that miR-214 expression levels were significantly increased not only in osteosarcoma tissues but also in osteosarcoma cell lines as compared with adjacent normal tissues and matched cell lines, respectively. On the contrary, the TRAF3 expression levels in osteosarcoma tissues and cell lines were frequently decreased compared to the control group. Moreover, TRAF3 was identified as a direct target of miR-214 and the inverse relationship between them was also observed in osteosarcoma tissues. Additionally, we found that miR-214 restoration could significantly promote osteosarcoma cell invasion and migration via targeting TRAF3.
MicroRNA-214 functioned as an oncogene in osteosarcoma via targeting TRAF3, which may provide new insights into osteosarcoma prevention and treatment.
骨肉瘤是一种发病率较高的恶性骨肿瘤。当骨肉瘤发生转移时,其预后非常差。大量研究表明,miRNA 的异常表达参与了癌症的发生和发展。然而,miR-214 在骨肉瘤中的潜在作用在很大程度上仍未被揭示。本研究探讨了 miR-214 与骨肉瘤组织和细胞系中肿瘤坏死因子受体相关因子 3(TRAF3)之间的关系。我们还旨在评估 miR-214 在骨肉瘤发生和转移中的潜在作用,并验证其对 TRAF3 调节的影响。
采用定量逆转录聚合酶链反应(qRT-PCR)检测骨肉瘤组织样本和细胞系中 miR-214 的表达和 TRAF3 的表达。通过转染实验,进行 Transwell 实验检测骨肉瘤细胞的迁移和侵袭能力。随后,在骨肉瘤细胞中进行 Western blot 和荧光素酶报告基因实验,以确认 miR-214 的靶标。
结果表明,miR-214 的表达水平不仅在骨肉瘤组织中显著升高,而且在骨肉瘤细胞系中也明显高于相邻正常组织和相应的细胞系。相反,与对照组相比,骨肉瘤组织和细胞系中的 TRAF3 表达水平经常下降。此外,TRAF3 被鉴定为 miR-214 的直接靶标,并且它们在骨肉瘤组织中也存在相反的关系。此外,我们发现 miR-214 的恢复可以通过靶向 TRAF3 显著促进骨肉瘤细胞的侵袭和迁移。
miR-214 通过靶向 TRAF3 在骨肉瘤中发挥癌基因作用,这可能为骨肉瘤的预防和治疗提供新的思路。