Wu Shun-Quan, Niu Wen-Yan, Li Ya-Ping, Huang Hao-Bo, Zhan Rong
Department of Hematology, Fujian Institute of Hematology, Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Department of Hematology, Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China.
Mol Med Rep. 2016 Nov;14(5):4795-4801. doi: 10.3892/mmr.2016.5832. Epub 2016 Oct 12.
The oncogene B-cell-specific Moloney murine leukemia virus insertion site‑1 (Bmi‑1) is overexpressed in multiple myeloma (MM). Our previous study demonstrated that Bmi‑1 silencing sensitized MM cells to bortezomib. Translational regulation has emerged as a prominent underlying mechanism of Bmi‑1 regulation, particularly via microRNA targeting. The present study determined that Bmi‑1 may be directly targeted by miR‑203 using a luciferase assay. In addition, enforced expression of miR-203 led to significant downregulation of Bmi‑1 protein and mRNA expression levels. Furthermore, restoration of miR-203 significantly inhibited cell growth and G1/S transition in MM cells. miR‑203 was downregulated in MM patients, and a negative correlation between the expression of miR‑203 and Bmi‑1 was observed. The results of the present study indicated that miR‑203 exerts growth‑inhibiting effects in MM through the suppression of Bmi‑1 expression. In conclusion, the present study demonstrated that Bmi‑1 is a direct functional target of miR-203 in MM.
致癌基因B细胞特异性莫洛尼鼠白血病病毒插入位点1（Bmi-1）在多发性骨髓瘤（MM）中过表达。我们之前的研究表明，Bmi-1沉默使MM细胞对硼替佐米敏感。翻译调控已成为Bmi-1调控的一个突出潜在机制，尤其是通过微小RNA靶向作用。本研究通过荧光素酶测定确定Bmi-1可能被miR-203直接靶向。此外，miR-203的强制表达导致Bmi-1蛋白和mRNA表达水平显著下调。此外，miR-203的恢复显著抑制MM细胞的生长和G1/S期转变。MM患者中miR-203表达下调，且观察到miR-203与Bmi-1表达之间呈负相关。本研究结果表明，miR-203通过抑制Bmi-1表达在MM中发挥生长抑制作用。总之，本研究证明Bmi-1是MM中miR-203的直接功能靶点。
