Abstract:Objective: To explore the impact of miR-145-5p targeting Survivin and the apoptotic signaling pathway on apoptosis, invasion, and migration in esophageal cancer.Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to detect the relative expression levels of miR-145-5p and Survivin mRNA in esophageal cancer tissues and cell lines. A dual-luciferase reporter gene analysis was conducted to validate the targeted regulatory relationship between miR-145-5p and Survivin. RT-qPCR was used to measure the relative expression levels of miR-145-5p and Survivin mRNA after cell transfection. Western blot was performed to assess the expression of BCL2, MDM2, and Caspase-3 proteins in the apoptotic pathway. Cell survival, apoptosis rate, migration rate, and invasion ability were evaluated using MTT, flow cytometry, scratch healing, and Transwell chamber experiments in TE-1 cells. Results: Compared to adjacent normal tissues, miR-145-5p was downregulated, while Survivin was upregulated in cancer tissues (P<0.05). In comparison to normal esophageal mucosal epithelial HEEC cells, TE-1 cells exhibited low expression of miR-145-5p and high expression of Survivin (P<0.05). Dual-luciferase reporter gene experiments confirmed the targeted regulatory relationship between miR-145-5p and Survivin. Transfection with miR-145-5p mimic significantly increased miR-145-5p expression, inhibited Survivin mRNA expression, downregulated BCL2 and MDM2 protein expression, upregulated Caspase-3 expression, promoted cell apoptosis, and inhibited cell viability, invasion, and migration compared to untransfected and miR-145-5p control-transfected TE-1 cells (P<0.05). Conclusion: Through negative regulation by miR-145-5p, the expression of Survivin is inhibited, leading to the activation of the apoptotic pathway. This promotes cell apoptosis and inhibits the survival, invasion, and migration capabilities of esophageal cancer cells.
郑竞雄, 杨阳, 孙光蕊, 赵宝山, 侯继申, 梁宗英, 王敏. miR-145-5p调控Survivin通过凋亡通路对食管癌生物学行为的影响[J]. 河北医学, 2024, 30(3): 386-392.
ZHENG Jingxiong, et al. Impact of miR-145-5p-Mediated Regulation of Survivin via the Apoptotic Pathway on the Biological Behavior of Esophageal Cancer. HeBei Med, 2024, 30(3): 386-392.
[1] Uhlenhopp DJ,Then EO,Sunkara T,et al.Epidemiology of esophageal cancer:update in global trends,etiology and risk factors[J].Clin Gastroenterol,2020,13(6):1010-1021. [2] Yang YM,Hong P,Xu WW,et al.Advances in targeted therapy for esophageal cancer[J].Signal Transduct Target Ther,2020,5(1):229-240. [3] 邢婉婷,徐静轩,齐鲁楠.MiR-145-5p靶向调控LOX基因对肝癌细胞侵袭和迁移的影响[J].中国癌症防治杂志,2022,14(1):26-32. [4] 伍春林,易鹏,黄祥,等.丁卡因通过MDM2基因下调Survivin蛋白抑制黑色素瘤生长[J].山西医科大学学报,2021,52(4):403-408. [5] 孙光蕊,杨阳,郑竞雄,等.Survivin通过Wnt/β-catenin信号通路调控食管癌的侵袭和迁移的机制研究[J].河北医学,2022,28(10):1620-1625. [6] 林晋,黄宇,唐风华,等.褪黑素通过调节survivin和Caspase-3表达诱导人骨肉瘤细胞凋亡[J].中国组织化学与细胞化学杂志,2020,29(1):28-33. [7] 赵宝忠,侯继申,张乐,等.食管癌Survivin乙酰化水平与PCAF P300表达的 相关性及临床意义[J].河北医学,2019,25(8):1377-1380. [8] Zeinali T,Mansoori B,Mohammadi A,et al.Regulatory mechanisms of miR-145 expression and the importance of its function in cancer metastasis[J].Biomed Pharmacother,2019,(109):195-207. [9] 封敏,艾比拜·莫合塔尔,石静怡,等.哈萨克族食管癌组织中miR-143、miR-145和 Survivin mRNA的表达及其临床病理意义[J].癌变·畸变·突变,2020,32(1):29-32. [10] 张雨薇,张馨,白立川,等.ceRNA调控miR-145-5p介导肿瘤发生发展的研究进展[J].现代肿瘤医学,2020,28(10):1766-1769. [11] Sun M,Zhao W,Chen Z,et al.Circ_0058063 regulates CDK6 to promote bladder cancer progression by sponging miR-145-5P[J].Cell Physiol,2019,234(4):4812-4824. [12] Zhou T,Chen S,Mao X.miR-145-5p affects the differentiation of gastric cancer by targeting KLF5 directly[J].Cell Physiol,2019,234(5):7634-7644. [13] 郭浩然,张涵,王鑫,等.细胞凋亡易感蛋白在恶性肿瘤中作用及机制的研究进展[J].中西医结合心脑血管病杂志,2022,20(14):2572-2575.