中文摘要
t(4;14)多发性骨髓瘤(MM)高表达MMSET蛋白,对化疗不敏感,易进展,其机制尚未明确。有研究显示t(4;14)MM中,存在一种核仁小分子RNA(small nucleolar RNAs, snoRNAs))- ACA11高表达,使MM细胞增殖,但其分子机制未明确。我们前期研究显示不仅t(4;14)MM患者ACA11高表达,且ISS分期Ⅱ或Ⅲ期的患者的ACA11表达水平更高,复发及疾病进展t(4;14)MM患者较初治时表达增多,MMSET没有直接调控ACA11表达的作用。最近研究证实snoRNAs具有microRNAs样的功能,因此,我们推测ACA11特异性调控靶基因,参与骨髓瘤的发生与发展。我们拟通过生物信息学技术,首先预测ACA11作用的靶基因,对靶基因进行验证,然后验证ACA11通过调控其靶基因而影响MM细胞增殖、侵袭能力,探讨ACA11在t(4;14)MM发生及发展中的作用。
英文摘要
Multiple myeloma (MM) with t(4;14) high express of MMSET protein, were resistant to chemotherapy and tend to progress. However, the mechanism of this is unknown. It’s reported that the MM patients and cell-lines with t(4;14), high express small nucleolar RNAs (snoRNAs )-ACA11, which let the MM cells get proliferation and get resistance to cytotoxic drugs. Also, the molecular mechanism of the snoRNAs is unclear. Our preliminary study has shown that ACA11 is high expressed in MM patients with t(4;14) and more higher expressed in the MM patients with high ISS stage(Ⅱ or Ⅲ). Compared with the newly diagnosed, the MM patients with t(4;14) at relapsed or progressed stage have a higher expression of ACA11,and the MMSET do not regulate the expression directly. The newest research showed that the snoRNAs had a mimic function of microRNAs. So we hypothesis that ACA11 may regulate the target gene specifically, and play an important role in the evolution and development of MM. In order to explore the role of ACA11 in the evolution and development of MM with t(4;14), here we will verify the target gene of ACA11, and verify the mechanism of how ACA11 regulate its target gene and affect the proliferation and resistant to chemotherapy of MM cells.
