Department of Radiation Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
Kaohsiung J Med Sci. 2019 May;35(5):277-283. doi: 10.1002/kjm2.12057. Epub 2019 Mar 21.
MicroRNA-26a (miR-26a) has been reported to be involved in the tumorigenesis of several tumors, but its biological function and molecular mechanism in multiple myeloma (MM) are still unknown. In this study, we found that overexpression of miR-26a obviously inhibited MM cell growth, and delayed tumor growth in xenografts. Further studies showed that overexpression of miR-26a induced cell cycle arrest at G0/G1 phase in MM cells. MiR-26a mimic down-regulated the expression levels of CDK6 and E2F1, but up-regulated p53 and p21 expression. In contrast, overexpression of CDK6 decreased the effect of miR-26a mimic on MM cell survival. Moreover, miR-26a targeted CDK6 mRNA and thus suppressed CDK6 protein expression. Overexpression of miR-26a also enhanced the cytotoxic action of doxorubicin against MM. These results demonstrated that miR-26a was involved in the development of MM through regulating CDK6 signaling pathway, and indicated that miR-26a could be as a novel target for anti-tumor therapy in clinic as a single strategy or in combination with other anti-tumor drugs in MM.
微小 RNA-26a（miR-26a）已被报道参与多种肿瘤的发生，但它在多发性骨髓瘤（MM）中的生物学功能和分子机制仍不清楚。在本研究中，我们发现 miR-26a 的过表达明显抑制了 MM 细胞的生长，并延迟了异种移植瘤的生长。进一步的研究表明，miR-26a 的过表达诱导 MM 细胞周期停滞在 G0/G1 期。miR-26a 模拟物下调 CDK6 和 E2F1 的表达水平，但上调 p53 和 p21 的表达。相反，CDK6 的过表达降低了 miR-26a 模拟物对 MM 细胞存活的影响。此外，miR-26a 靶向 CDK6 mRNA，从而抑制 CDK6 蛋白表达。miR-26a 的过表达还增强了阿霉素对 MM 的细胞毒性作用。这些结果表明，miR-26a 通过调节 CDK6 信号通路参与 MM 的发生，表明 miR-26a 可以作为一种新型的治疗靶点，作为单一策略或与其他抗肿瘤药物联合应用于 MM 的抗肿瘤治疗。
