A novel hypoxic lncRNA, HRL-SC, promotes the proliferation and migration of human dental pulp stem cells through the PI3K/AKT signaling pathway.
A novel hypoxic lncRNA, HRL-SC, promotes the proliferation and migration of human dental pulp stem cells through the PI3K/AKT signaling pathway.
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新型缺氧lncRNA HRL-SC通过PI3K/AKT信号通路促进人牙髓干细胞增殖和迁移
DOI：
10.1186/s13287-022-02970-5
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发表时间：
2022-06-28
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
人牙髓干细胞（Human dental pulp stem cells，hDPSC）是牙髓形成的关键细胞。hDPSC在缺氧条件下增殖更快，但长链非编码RNA（lncRNA）调节这一过程的机制尚未完全了解。通过在缺氧条件下与常氧条件下相比重新分析来自RNA-Seq的转录组数据集获得新的lncRNA，并进行靶基因的差异表达分析。生物信息学分析包括基因本体分析、京都基因百科全书和基因组途径分析和基因集富集分析，用于了解关键新lncRNA的功能。从牙髓组织中分离hDPSC。EdU和划痕伤口愈合测定用于检测hDPSC的增殖和迁移。使用qRT-PCR检测所选基因的RNA表达的变化。采用RNA荧光原位杂交、小干扰RNA、qRT-PCR和Western印迹分析来探索关键新型lncRNA的功能。我们在缺氧条件下的hDPSC中鉴定了496个新的lncRNA，其中包括45个差异表达的新lncRNA。其中，我们专注于一种关键的新型lncRNA，我们将其命名为HRL-SC（干细胞中的低氧反应lncRNA）。功能注释显示HRL-SC与缺氧条件和PI 3 K/AKT信号通路相关。HRL-SC主要定位于hDPSCs的胞浆中，在缺氧条件下有稳定的高表达。HRL-SC的敲低可抑制hDPSC的增殖和迁移，并抑制PI 3 K/AKT相关标志蛋白的表达。此外，AKT激活剂SC 79部分抵消了由敲低引起的抑制作用，表明HRL-SC通过PI 3 K/AKT信号通路促进hDPSC。缺氧反应性lncRNA HRL-SC通过PI 3 K/AKT信号通路促进hDPSC的增殖和迁移，这一认识可能有助于hDPSC的再生应用。在线版本包含补充材料，可通过10.1186/s13287-022-02970-5获得。
Human dental pulp stem cells (hDPSCs) are critical for pulp generation. hDPSCs proliferate faster under hypoxia, but the mechanism by which long noncoding RNA (lncRNA) regulates this process is not fully understood. Novel lncRNAs were obtained by reanalysis of transcriptome datasets from RNA-Seq under hypoxia compared with normoxia, and a differential expression analysis of target genes was performed. Bioinformatics analyses, including gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and gene set enrichment analysis, were used to understand the function of key novel lncRNAs. hDPSCs were isolated from dental pulp tissue. EdU and scratch wound healing assays were used to detect the proliferation and migration of hDPSCs. qRT-PCR was used to detect changes in the RNA expression of selected genes. RNA fluorescence in situ hybridization, small interfering RNA, qRT-PCR and Western blot analysis were used to explore the function of key novel lncRNAs. We identified 496 novel lncRNAs in hDPSCs under hypoxia, including 45 differentially expressed novel lncRNAs. Of these, we focused on a key novel lncRNA, which we designated HRL-SC (hypoxia-responsive lncRNA in stem cells). Functional annotation revealed that HRL-SC was associated with hypoxic conditions and the PI3K/AKT signaling pathway. HRL-SC was mainly located in the cytoplasm of hDPSCs and had stable high expression under hypoxia. Knockdown of HRL-SC inhibited the proliferation and migration of hDPSCs and the expression levels of PI3K/AKT-related marker proteins. Furthermore, the AKT activator SC79 partially offset the inhibitory effect caused by the knockdown, indicating that HRL-SC promoted hDPSCs through the PI3K/AKT signaling pathway. Hypoxia-responsive lncRNA HRL-SC promotes the proliferation and migration of hDPSCs through the PI3K/AKT signaling pathway, and this understanding may facilitate the regenerative application of hDPSCs. The online version contains supplementary material available at 10.1186/s13287-022-02970-5.
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DOI：
10.12659/msm.910191
发表时间：
2018-08-03
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Luan Q;Pan L;He D;Gong X;Zhou H
通讯作者：
Zhou H
影响因子：
--
作者：
Bhandi S;Al Kahtani A;Mashyakhy M;Alsofi L;Maganur PC;Vishwanathaiah S;Testarelli L;Del Giudice A;Mehta D;Vyas N;Patil VR;Raj AT;Patil S
通讯作者：
Patil S
长非编码RNA H19通过抑制miR-199a-5p上调血管内皮生长因子A以增强间充质干细胞的存活和血管生成能力
影响因子：
7.5
作者：
Hou, Jingying;Wang, Lingyun;Wang, Tong
通讯作者：
Wang, Tong
影响因子：
3
作者：
Iida, Kazuki;Takeda-Kawaguchi, Tomoko;Tezuka, Ken-ichi
通讯作者：
Tezuka, Ken-ichi
影响因子：
7.6
作者：
Huang GT;Gronthos S;Shi S
通讯作者：
Shi S