Zhang Qi, Yan Weiqun, Bai Yang, Xu Hao, Fu Changhao, Zheng Wenwen, Zhu Yingqiao, Ma Jie
School of Pharmaceutical Sciences, Jilin University, Jilin, P.R. China.
First Hospital of Jilin University, Jilin, P.R. China.
Oncol Rep. 2015 Jan;33(1):448-56. doi: 10.3892/or.2014.3591. Epub 2014 Nov 5.
Multiple myeloma (MM) is a disease with an adverse outcome and new therapeutic strategies are required to combat this disease. It is well known that tumor‑suppressor microRNA (miRNA) acts as a new potential anticancer agent. Accumulating evidence showed that microRNA-145 (miR-145) is a candidate tumor suppressor miRNA. However, whether miR-145 is involved in the development and progression of MM reamins to be determined. In the present study, we investigated the therapeutic potential of synthetic miR-145 against human MM cells in vitro and in vivo. The results showed that miR-145 was reduced in MM tissues and cell lines. Enforced expression of miR-145 by transfection with miR-145 mimics inhibited cell proliferation, migration, and the invasion abilities of H929 cells. Furthermore, our results demonstrated that the enforced expression of miR-145 in H929 cells profoundly decreased the levels of p-AKT and p-PI3K, which may contribute to some extent to the inhibition of MM cell proliferation and survival. The enforced expression of miR-145 in a xenograft mouse model suppressed tumor growth. In conclusion, our findings suggested that miR-145 may act as a tumor suppressor and contributes to the progression of MM. Additionally, miR-145 mimics is a potential therapeutic agent for the treatment of MM.
多发性骨髓瘤（MM）是一种预后不良的疾病，需要新的治疗策略来对抗这种疾病。众所周知，肿瘤抑制性微小RNA（miRNA）作为一种新的潜在抗癌剂。越来越多的证据表明，微小RNA-145（miR-145）是一种候选肿瘤抑制性miRNA。然而，miR-145是否参与MM的发生发展仍有待确定。在本研究中，我们在体外和体内研究了合成miR-145对人MM细胞的治疗潜力。结果表明，miR-145在MM组织和细胞系中表达降低。通过转染miR-145模拟物强制表达miR-145可抑制H929细胞的增殖、迁移和侵袭能力。此外，我们的结果表明，在H929细胞中强制表达miR-145可显著降低p-AKT和p-PI3K的水平，这可能在一定程度上有助于抑制MM细胞的增殖和存活。在异种移植小鼠模型中强制表达miR-145可抑制肿瘤生长。总之，我们的研究结果表明，miR-145可能作为一种肿瘤抑制因子，并参与MM的进展。此外，miR-145模拟物是治疗MM的一种潜在治疗剂。
