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Impact of miR-145-5p-Mediated Regulation of Survivin via the Apoptotic Pathway on the Biological Behavior of Esophageal Cancer |
ZHENG Jingxiong, et al |
The Affiliated Hospital of Chengde Medical University, Hebei Chengde 067000, China |
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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.
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[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. |
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