Yu Tianhua, Zhang Xuanhe, Zhang Lirong, Wang Yali, Pan Hongjuan, Xu Zhihua, Pang Xiaochuan
Department of Blood Transfusion, China-Japan Union Hospital of Jilin University 126 Xiantai Street, Changchun 130033, China.
Shihezi University 221 North Fourth Road, Shihezi 832003, China.
Am J Cancer Res. 2016 Dec 1;6(12):2880-2889. eCollection 2016.
Aberrant expression of microRNA-497 (miRN-497) is implicated in development and progression of multiple types of cancers. However, the biological function and underlying mechanism of miR-497 in multiple myeloma (MM) remains unclear. Thus, we studied the potential biological roles of miR-497 in MM. The expression of miR-497 was examined in multiple myeloma and normal plasma cells by qRT-PCR. Biological functions of miR-497 were analyzed using cell proliferation, colony formation, cell cycle, apoptosis and luciferase assays , as well as via tumorigenicity analysis. Here, we observed reduced expression of miR-497 in MM plasma samples and cell lines. Ectopic expression of miR-497 dramatically suppressed cell proliferation and clonogenicity, as well as induced cell arrest at G0/G1 stage and apoptosis . Mechanistic investigation assays showed that Pre-B-cellleukemia transcription factor 3 (PBX3) was a novel and direct downstream target of miR-497. Interestingly, overexpression of PBX3 partially reverted the effect of miR-497 in MM cells. In xenograft model, overexpression of miR-497 inhibited tumorigenicity by repressing PBX3. These findings collectively suggested that miR-497 functioned as tumor suppressor in MM by directly targeting PBX3, supporting its utility as a novel and potential therapeutic agent for MM therapy.
微小RNA-497（miR-497）的异常表达与多种癌症的发生发展有关。然而，miR-497在多发性骨髓瘤（MM）中的生物学功能及潜在机制仍不清楚。因此，我们研究了miR-497在MM中的潜在生物学作用。通过qRT-PCR检测多发性骨髓瘤和正常浆细胞中miR-497的表达。使用细胞增殖、集落形成、细胞周期、凋亡和荧光素酶检测以及致瘤性分析来分析miR-497的生物学功能。在此，我们观察到MM血浆样本和细胞系中miR-497表达降低。miR-497的异位表达显著抑制细胞增殖和克隆形成能力，并诱导细胞停滞在G0/G1期和凋亡。机制研究检测表明，前B细胞白血病转录因子3（PBX3）是miR-497新的直接下游靶点。有趣的是，PBX3的过表达部分逆转了miR-497对MM细胞的作用。在异种移植模型中，miR-497的过表达通过抑制PBX3抑制致瘤性。这些发现共同表明，miR-497通过直接靶向PBX3在MM中发挥肿瘤抑制作用，支持其作为MM治疗的新型潜在治疗药物的应用价值。
