Exosome-transmitted LINC00461 promotes multiple myeloma cell proliferation and suppresses apoptosis by modulating microRNA/BCL-2 expression
Exosome-transmitted LINC00461 promotes multiple myeloma cell proliferation and suppresses apoptosis by modulating microRNA/BCL-2 expression
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DOI：
10.1016/j.jcyt.2018.10.006
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发表时间：
2019-01-01
期刊：
影响因子：
4.5
通讯作者：
Xiao, Han
中科院分区：
文献类型：
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作者：
Deng, Mingyang;Yuan, Huan;Xiao, Han
背景：多发性骨髓瘤（Multiple myeloma， MM）是一种由浆细胞异常扩张引起的血液学癌症，但其发展的确切机制尚不完全清楚。近年来，多种长链非编码rna （lncrna）参与了mm2发育的调控。方法：采集MM患者标本，采用实时聚合酶链反应（real-time polymerase chain reaction， PCR）检测LINC00461的表达。利用短发夹rna （short hairpin RNAs, shRNAs）在MM细胞系中敲低LINC00461，检测其对MM细胞增殖和凋亡的影响。采用室法分析间充质基质细胞（MSC）衍生外泌体的功能。结果：LINC00461在MM中高表达，敲低LINC00461可显著降低MM细胞增殖，诱导细胞凋亡。进一步研究表明，LINC00461缓解了microRNA (miR)-15a/miR-16对BCL-2的抑制作用。此外，我们观察到msc来源的外泌体通过LINC00461促进MM细胞增殖。结论：我们的研究结果表明，LINC00461， miR-15a/16的海绵，在msc来源的外泌体中高表达，并增强MM细胞的增殖，可能成为治疗应用的优秀候选者。
Background: Multiple myeloma (MM) is a hematologic cancer caused by the abnormal expansion of plasma cells, but the exact mechanism underlying MM development is not completely known. Recently, multiple long noncoding RNAs (lncRNAs) were implicated in the regulation of MMdevelopment. Methods: Samples from patients with MM were collected and detected for LINC00461 expression using real-time polymerase chain reaction (PCR). LINC00461 was knocked down in MM cell lines by short hairpin RNAs (shRNAs) to measure its effect on MM cell proliferation and apoptosis. The function of mesenchymal stromal cell (MSC)-derived exosomes was analyzed using chamber assays. Results: LINC00461 was highly expressed in MM. Knockdown of LINC00461 dramatically reduced MM cell proliferation and induced cell apoptosis. Further study showed that LINC00461 relieved the inhibitory effect of microRNA (miR)-15a/miR-16 on BCL-2. In addition, we observed that MSC-derived exosomes promoted MM cell proliferation through LINC00461. Conclusion: Our findings demonstrate that LINC00461, a sponge for miR-15a/16, is highly expressed in MSC-derived exosomes, and enhances MM cell proliferation, which may become an excellent candidate for therapeutic applications.