Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
Cytotherapy. 2019 Jan;21(1):96-106. doi: 10.1016/j.jcyt.2018.10.006. Epub 2018 Nov 5.
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 MM development.
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.
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.
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.
多发性骨髓瘤（MM）是一种由浆细胞异常增殖引起的血液系统恶性肿瘤，但 MM 发展的确切机制尚不完全清楚。最近，多个长链非编码 RNA（lncRNA）被认为参与了 MM 发育的调控。
采用实时聚合酶链反应（PCR）检测 MM 患者样本中 LINC00461 的表达。利用短发夹 RNA（shRNA）敲低 MM 细胞系中的 LINC00461，以测量其对 MM 细胞增殖和凋亡的影响。利用室试验分析间充质基质细胞（MSC）衍生的外泌体的功能。
LINC00461 在 MM 中高表达。敲低 LINC00461 可显著降低 MM 细胞的增殖并诱导细胞凋亡。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 衍生的外泌体通过 LINC00461 促进 MM 细胞增殖。
我们的研究结果表明，LINC00461 作为 miR-15a/16 的海绵，在 MSC 衍生的外泌体中高表达，并增强 MM 细胞增殖，这可能成为治疗应用的一个优秀候选者。
