Duan Qunjun, Dong Aiqiang, Cheng Haifeng, Zhang Shufen, Chen Wei, Yang Weijun
Department of Cardiaovascular Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Department of Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, China.
Comb Chem High Throughput Screen. 2025;28(1):110-121. doi: 10.2174/0113862073267559231106074309.
Taurine upregulated gene 1 (TUG1) has been identified on long noncoding RNA (lncRNA); however, its function in myocardial cells following ischemia/ reperfusion (I/R) injury has not been explored. This study aimed to investigate the role of LncTUG1 in I/R injury by focusing on its relationship with autophagy induction by regulating miR-34a-5p expression.
We established a myocardial I/R model and H9C2 hypoxia-ischemic and reoxygenation (HI/R) conditions to induce I/R injury. TTC, Western blot, CCK-8 assay, quantitative reverse transcription PCR, flow cytometry, and confocal microscopy were used to assess the size of myocardial infarct, level of some apoptotic-related and autophagy-associated proteins, cell viability, the level of LncRNA TUG1, apoptosis, and autophagy, respectively.
The results revealed that a TUG1 knockdown protected against I/R-induced myocardial injury by decreasing the impairment in cardiac function. LncRNA TUG1 expression was increased in a myocardial I/R model and HI/R in H9C2 cells. Moreover, inhibition of LncTUG1 enhanced H9C2 cell viability and protected the cells from HI/R-induced apoptosis. Silencing LncRNA TUG1 promoted HI/R-induced autophagy. Furthermore, TUG1 siRNA upregulated the level of miR-34a-5p compared to the HI/R group. The protective effect of LncRNA TUG1 inhibition on H9C2 cells following HI/R was eliminated by blocking autophagy with an miR-34a-5p inhibitor.
These findings indicated that inhibiting TUG1 may reduce the extent of myocardial I/R injury by regulating miR-34a-5p. Taken together, these results suggest that LncRNA TUG1 may represent a novel therapeutic target for myocardial I/R injury.
牛磺酸上调基因1（TUG1）已被鉴定为长链非编码RNA（lncRNA）；然而，其在缺血/再灌注（I/R）损伤后心肌细胞中的功能尚未得到研究。本研究旨在通过关注其与调节miR-34a-5p表达诱导自噬的关系，探讨LncTUG1在I/R损伤中的作用。
我们建立了心肌I/R模型以及H9C2细胞缺氧缺血再复氧（HI/R）条件以诱导I/R损伤。采用TTC、蛋白质免疫印迹法、CCK-8检测、定量逆转录PCR、流式细胞术和共聚焦显微镜分别评估心肌梗死面积、一些凋亡相关和自噬相关蛋白的水平、细胞活力、LncRNA TUG1水平、凋亡和自噬。
结果显示，敲低TUG1可通过减轻心脏功能损害来预防I/R诱导的心肌损伤。在心肌I/R模型和H9C2细胞的HI/R中，LncRNA TUG1表达增加。此外，抑制LncTUG1可提高H9C2细胞活力，并保护细胞免受HI/R诱导的凋亡。沉默LncRNA TUG1可促进HI/R诱导的自噬。此外，与HI/R组相比，TUG1 siRNA上调了miR-34a-5p的水平。用miR-34a-5p抑制剂阻断自噬可消除LncRNA TUG1抑制对HI/R后H9C2细胞的保护作用。
这些发现表明，抑制TUG1可能通过调节miR-34a-5p来降低心肌I/R损伤的程度。综上所述，这些结果表明LncRNA TUG1可能是心肌I/R损伤的一个新的治疗靶点。
