Lnc-AC145676.2.1-6-3 can influence STX3-induced abnormal autophagy by sponging hsa-miR-1292-3p in intestinal aGVHD

X.-Q. Sun, G.-Q. Tan, Z. Gao, X.-J. Liu, M.-T. Xia, Y.-Y. Zhang, R.-J. Sun, X. Cui

Department of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. cdz45@foxmail.com

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• Autoimmunity
• Immunology

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.

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