长链非编码 RNA KCNQ1OT1 通过调节 miR-421-3p/mTOR 轴减轻绝经后骨质疏松症,Scientific Reports

当前位置： X-MOL 学术 › Sci. Rep. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

长链非编码 RNA KCNQ1OT1 通过调节 miR-421-3p/mTOR 轴减轻绝经后骨质疏松症
Scientific Reports ( IF 3.8 ) Pub Date : 2023-02-09 , DOI: 10.1038/s41598-023-29546-4
Ziyu Wang _{1,

2} , Hengshuo Zhang _{1,

2} , Qinghui Li _{1,

2} , Lu Zhang _{1,

2} , Lu Chen ₂ , Hongliang Wang ₁ , Yunzhen Chen _{1,

2}

Affiliation

绝经后骨质疏松症（PMOP）的防治是一个重大的公共卫生问题，非编码RNA在这一过程中至关重要。在这项研究中，我们发现长链非编码 RNA 钾电压门控通道亚家族 Q 成员 1 重叠转录本 1 (lncRNA KCNQ1OT1) 可以减轻体内卵巢切除术 (OVX) 引起的 PMOP。我们确定 KCNQ1OT1 的过表达可以增强 MC3T3-E1 细胞的功能，而当 KCNQ1OT1 被击倒时观察到相反的趋势。随后，通过数据库搜索检测到靶向KCNQ1OT1的miR-421-3p，RNA荧光原位杂交、RNA免疫沉淀、双荧光素酶报告基因检测均证实了这种关系。值得注意的是，KCNQ1OT1 抑制了 miR-421-3p 的表达。抑制增殖、迁移、miR-421-3p 抑制剂可逆转 KCNQ1OT1 敲低引起的成骨分化，进一步证实了上述发现。我们验证了 miR-421-3p 特异性靶向雷帕霉素 (mTOR) 的哺乳动物靶标，并且 miR-421-3p 抑制剂可以逆转 mTOR (si-mTOR) 的小干扰 RNA 对 MC3T3-E1 细胞的负面影响。最后，从 OVX 小鼠模型和对照小鼠中分离和培养的成骨细胞也证实了观察到的趋势。综上所述，上述结果表明 KCNQ1OT1 通过调节 miR-421-3p/mTOR 轴来调节 MC3T3-E1 细胞功能。miR-421-3p抑制剂可逆转mTOR小分子干扰RNA（si-mTOR）对MC3T3-E1细胞的负面影响。最后，从 OVX 小鼠模型和对照小鼠中分离和培养的成骨细胞也证实了观察到的趋势。综上所述，上述结果表明 KCNQ1OT1 通过调节 miR-421-3p/mTOR 轴来调节 MC3T3-E1 细胞功能。miR-421-3p抑制剂可逆转mTOR小分子干扰RNA（si-mTOR）对MC3T3-E1细胞的负面影响。最后，从 OVX 小鼠模型和对照小鼠中分离和培养的成骨细胞也证实了观察到的趋势。综上所述，上述结果表明 KCNQ1OT1 通过调节 miR-421-3p/mTOR 轴来调节 MC3T3-E1 细胞功能。

"点击查看英文标题和摘要"

Long non-coding RNA KCNQ1OT1 alleviates postmenopausal osteoporosis by modulating miR-421-3p/mTOR axis

The prevention and treatment of postmenopausal osteoporosis (PMOP) is a significant public health issue, and non-coding RNAs are of vital importance in this process. In this study, we find that the long non-coding RNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (lncRNA KCNQ1OT1) can alleviate the ovariectomy-induced (OVX) PMOP in vivo. We determined that over-expression of KCNQ1OT1 could enhance functions of MC3T3-E1 cells, whereas an opposite trend was observed when KCNQ1OT1 was knocked down. Subsequently, miR-421-3p targeting KCNQ1OT1 was detected through a database search, and RNA fluorescent in situ hybridization, RNA immunoprecipitation, dual luciferase reporter assays all verified this relationship. Notably, KCNQ1OT1 stifled the miR-421-3p expression. The inhibition of proliferation, migration, and osteogenic differentiation caused by KCNQ1OT1 knock-down were reversed by an miR-421-3p inhibitor, further confirming the above findings. We verified that miR-421-3p specifically targeted the mammalian target of rapamycin (mTOR), and miR-421-3p inhibitor could reverse the negative effects of small interfering RNA of mTOR (si-mTOR) on MC3T3-E1 cells. Finally, osteoblasts isolated and cultured from OVX mice model and control mice also confirmed the observed trend. In combination, results mentioned above reveal that KCNQ1OT1 regulates MC3T3-E1 cell functions by regulating the miR-421-3p/mTOR axis.

更新日期：2023-02-09

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南