MicroRNA-19a functions as an oncogene by regulating PTEN/AKT/pAKT pathway in myeloma
MicroRNA-19a functions as an oncogene by regulating PTEN/AKT/pAKT pathway in myeloma
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DOI：
10.1080/10428194.2016.1213827
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发表时间：
2017-01-01
影响因子：
2.6
通讯作者：
Wang, Xiaofang
中科院分区：
文献类型：
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作者：
Zhang, Xiaoying;Chen, Yafang;Wang, Xiaofang
MicroRNA (miRNA) 与包括骨髓瘤在内的人类癌症有关。 MiR-19a 是致癌 miR-17-92 簇之一，被确定为许多癌症的关键致癌成分。然而，miR-19a在骨髓瘤中的功能尚未完全阐明。本研究的目的是探讨 miR-19a 在 MM 中的生物学功能。在体外，我们检测到 miR-19a-3p 在骨髓瘤细胞中过度表达。分别通过MTT和BD基质胶测定分析骨髓瘤细胞的增殖和内观。通过Western blot检测转染miR-19a-3p后骨髓瘤细胞中凋亡/耐药相关主控蛋白BCL-2和MDR1的表达情况。最后，我们发现miR-19a通过促进细胞增殖/浸润和抑制细胞凋亡作为MM中的癌基因。此外，我们进一步发现，miR-19a表达升高后，BCL-2和MDR的mRNA和蛋白显着上调，该过程受到PTEN/AKT/pAKT信号通路的调控。我们的结果表明，miR-19a 通过靶向骨髓瘤中的 PTEN 作为致癌 miRNA。这种新型 miR-19a/PTEN/AKT 轴为细胞凋亡和视觉机制提供了新的线索，并可能为骨髓瘤的治疗提供潜在的治疗靶点。
MicroRNAs (miRNAs) are involved in human cancers including myeloma. MiR-19a is one of the oncogenic miR-17-92 clusters, which is identified as a key oncogenic component in many cancers. Nevertheless, the function of miR-19a in myeloma has not been totally elucidated. The purpose of this study is to investigate the biological functions of miR-19a in MM. In vitro, we detected that the miR-19a-3p is overexpressed in myeloma cells. The proliferation and invision of myeloma cells are analyzed by MTT and BD matrigel assays, respectively. Western blot was performed to evaluate the expression of apoptotic/drug resistance-related main control proteins BCL-2 and MDR1 in myeloma cells after transfected with miR-19a-3p.Finally, we found miR-19a acts as an oncogene in MM by promoting cell proliferation/invision and inhibiting apoptosis. Additionally, We further showed that the mRNA and protein of BCL-2 and MDR were upregulated significantly after elevated expression of miR-19a, the process of which was regulated by PTEN/AKT/pAKT-signaling pathway. Our results suggest that miR-19a acted as an oncogenic miRNA by targeting PTEN in myeloma. This novel miR-19a/PTEN/AKT axis sheds new light on the mechanisms underlying apoptosis and invision and may provide potentially therapeutic targets for the treatment of myeloma.