Lnc-AC145676.2.1-6-3 can influence STX3-induced abnormal autophagy by sponging hsa-miR-1292-3p in intestinal aGVHD
Lnc-AC145676.2.1-6-3 can influence STX3-induced abnormal autophagy by sponging hsa-miR-1292-3p in intestinal aGVHD
复制标题
Lnc-AC145676.2.1-6-3可以通过在肠道aGVHD中海绵hsa-miR-1292-3p来影响STX3诱导的异常自噬
DOI：
10.26355/eurrev_202201_27884
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
X. CUI
中科院分区：
文献类型：
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作者：
X.-Q. SUN;G.-Q. TAN;Z. GAO;X.-J. LIU4;M.-T. XIA;Y.-Y. ZHANG;R.-J. SUN;X. CUI
目的：肠道急性移植物抗宿主病(AGVHD)是异基因造血干细胞移植(allo-HSCT)的严重并发症。许多研究证实，肠道aGVHD的自噬水平异常。LncRNAs发挥协同调节功能，参与多种细胞内调节过程。在本研究中，我们研究了lnc-AC145676.2.1-6-3对aGVHD中STX3相关自噬的调节作用。材料和方法：首先，我们通过将经60CoX射线处理的Balb/c供体小鼠的单个核细胞悬液移植到CB6F1受体小鼠体内，建立了aGVHD小鼠模型。通过Western blotting(WB)和免疫组织化学分析STX3相关指标，证实STX3在肠道aGVHD自噬功能失调中起重要作用。建立肿瘤坏死因子-α诱导的Caco-2细胞肠屏障功能障碍的体外模型，以验证其作用。用双荧光素酶活性测定评价LNC-AC145676.2.1-6-3介导的hsa-miR-1292-3p与STX3轴的直接相互作用。结果：LNC-AC145676.2.1-6-3可通过上调STX3水平，显著抑制Caco-2细胞自噬空泡数、Lc3-II/I比值和Beclin1水平。结论：LNC-AC145676.2.1-6-3可能通过靶向STX3而在AGVHD中发挥重要作用。
Objective: Intestinal acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Abnormal autophagy levels in intestinal aGVHD have been confirmed in many studies. LncRNAs exert coregulatory functions and participate in a variety of intracellular regulatory processes. In this study, we investigated how lnc-AC145676.2.1-6-3 regulates dysregulated STX3-related autophagy in aGVHD..Materials and methods: First, we established a mouse model of aGVHD by transplanting a mononuclear cell suspension from Balb/c donor mice treated with 60Co X-rays into CB6F1 recipient mice. STX3-related indicators were analyzed by Western blotting (WB) and immunohistochemistry which confirmed that STX3 plays an important role in dysregulating autophagy in intestinal aGVHD. TNF-αinduced Caco-2 cells, which is an in vitro model of intestinal barrier dysfunction, were established to verify the effect of STX3. The direct interaction between the partners of lnc-AC145676.2.1-6-3-mediated hsa-miR-1292-3p and STX3 axis was evaluated by the Dual-Luciferase activity assay. We performed PCR, WB, and immunofluorescence in Caco-2 cells to determine whether the abnormal autophagy levels were influenced by lnc-AC145676.2.1-6-3..Results: The results showed that lnc-AC145676.2.1-6-3 could significantly suppress the number of autophagic vacuoles, the LC3-II/I ratio, and beclin1 levels by increasing STX3 levels..Conclusions: Lnc-AC145676.2.1-6-3 may play an important role in intestinal aGVHD by targeting STX3.