Long Shifeng, Long Shengping, He Honglei, Chen Guoan
Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Hematology, The Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi 343000, P.R. China.
Exp Ther Med. 2019 Jun;17(6):4741-4747. doi: 10.3892/etm.2019.7473. Epub 2019 Apr 10.
Increasing evidence has revealed that microRNAs (miRNAs) are closely associated with multiple myeloma (MM) pathogenesis and progression. Therefore, an in-depth understanding of the biological functions of miRNAs in MM may be helpful for the identification of promising therapeutic techniques for patients with MM. miRNA-765 (miR-765) has been reported to be dysregulated in many types of human cancer. However, the expression pattern, specific roles and underlying mechanisms of miR-765 in MM remain largely unknown. In the present study, plasma miR-765 significantly increased in patients with MM and cell lines. The downregulation of miR-765 in MM cells attenuated proliferation and promoted apoptosis. Bioinformatics analysis predicted that SRY-Box 6 (SOX6) was a putative target of miR-765. This was experimentally verified using a luciferase reporter assay, reverse transcription-quantitative PCR and western blot analysis. Furthermore, plasma SOX6 was downregulated in patients with MM and the downregulation of SOX6 was inversely correlated with that of miR-765 expression. Furthermore, SOX6 knockdown markedly abrogated the effects of miR-765 underexpression on cell proliferation and apoptosis in MM. The current study demonstrated that miR-765 serves an oncogenic role in MM progression by directly targeting SOX6, suggesting that miR-765 may be a potential therapeutic target for MM prevention and treatment.
越来越多的证据表明,微小RNA(miRNA)与多发性骨髓瘤(MM)的发病机制和进展密切相关。因此,深入了解miRNA在MM中的生物学功能可能有助于为MM患者确定有前景的治疗技术。据报道,miRNA-765(miR-765)在多种人类癌症中表达失调。然而,miR-765在MM中的表达模式、具体作用及潜在机制仍 largely 未知。在本研究中,MM患者及细胞系中的血浆miR-765显著升高。MM细胞中miR-765的下调减弱了增殖并促进了凋亡。生物信息学分析预测,SRY-Box 6(SOX6)是miR-765的一个假定靶标。通过荧光素酶报告基因检测、逆转录定量PCR和蛋白质印迹分析对其进行了实验验证。此外,MM患者血浆中的SOX6下调,且SOX6的下调与miR-765表达的下调呈负相关。此外,敲低SOX6显著消除了miR-765低表达对MM细胞增殖和凋亡的影响。当前研究表明,miR-765通过直接靶向SOX6在MM进展中发挥致癌作用,提示miR-765可能是MM预防和治疗的一个潜在治疗靶点。