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Hsa_circ_0023984 通过调控 miR-1294/PI3K/Akt/c-Myc 通路调节食管鳞癌细胞增殖、迁移和侵袭。

Hsa_circ_0023984 Regulates Cell Proliferation, Migration, and Invasion in Esophageal Squamous Cancer via Regulating miR-1294/PI3K/Akt/c-Myc Pathway.

机构信息

Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Jianshedong Road No.1, Zhengzhou, 450000, Henan, China.

Department of Oncology, Anyang Tumor Hospital, the Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Henan Medical Key Laboratory of Precise Prevention and Treatment of Esophageal Cancer, Anyang, 455000, Henan, China.

出版信息

Appl Biochem Biotechnol. 2022 Sep;194(9):1-16. doi: 10.1007/s12010-022-03935-3. Epub 2022 May 6.

Abstract

Circular RNAs (circRNAs) exert an essential function in the tumorigenesis and progression of esophageal squamous cancer (ESCC). Nonetheless, the role and potential mechanism of circ_0023984 in ESCC are blurred. circRNA expression profile data from Gene Expression Omnibus (GEO) database was applied to analyze circRNAs that were differentially expressed between ESCC tissues and paracancerous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze circ_0023984 expression and miR-1294 expression in ESCC tissues and cells. Then a series of functional experiments were executed to validate the role of circ_0023984 and miR-1294 in modulating the proliferation, migration, invasion, and cell cycle progression of ESCC cells. Luciferase reporter experiment was performed to confirm the targeting relationship between circ_0023984 and miR-1294. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out with DAVID database. Western blot assay was utilized to detect phosphorylated-Akt (p-Akt) expression and c-Myc expression. circ_0023984 was remarkably upmodulated in ESCC tumor tissues and cell lines. circ_0023984 overexpression was correlated with advanced clinical stage and lymph node metastasis of ESCC patients. circ_0023984 overexpression remarkably enhanced ESCC cell proliferation, migration, invasion, and cell cycle progression, while knockdown of circ_0023984 showed the opposite effect. circ_0023984 was the molecular sponge of miR-1294. miR-1294 could significantly inhibit ESCC cell proliferation, migration, invasion, and induce cell cycle arrest at G0/G1 phase. circ_0023984 affected ESCC progression through regulating miR-1294 expression. The target genes of miR-1294 were associated with cell cycle arrest and PI3K-Akt signaling pathway. circ_0023984 upregulated the expression of p-Akt and c-Myc by repressing miR-1294. circ_0023984 facilitates the malignant biological behaviors of ESCC cells through inhibiting miR-1294 and activating PI3K/Akt/c-myc pathway.

摘要

环状 RNA(circRNAs)在食管鳞状细胞癌(ESCC)的发生和发展中发挥着重要作用。然而,circ_0023984 在 ESCC 中的作用和潜在机制尚不清楚。我们应用基因表达综合数据库(GEO)数据库中的环状 RNA 表达谱数据来分析 ESCC 组织和癌旁组织之间差异表达的环状 RNA。采用实时定量聚合酶链反应(qRT-PCR)检测 ESCC 组织和细胞中 circ_0023984 和 miR-1294 的表达。然后进行一系列功能实验来验证 circ_0023984 和 miR-1294 在调节 ESCC 细胞增殖、迁移、侵袭和细胞周期进展中的作用。荧光素酶报告实验证实 circ_0023984 与 miR-1294 之间的靶向关系。使用 DAVID 数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。Western blot 检测磷酸化-Akt(p-Akt)和 c-Myc 的表达。circ_0023984 在 ESCC 肿瘤组织和细胞系中显著上调。circ_0023984 的过表达与 ESCC 患者的晚期临床分期和淋巴结转移相关。circ_0023984 的过表达显著增强了 ESCC 细胞的增殖、迁移、侵袭和细胞周期进程,而 circ_0023984 的敲低则表现出相反的效果。circ_0023984 是 miR-1294 的分子海绵。miR-1294 可显著抑制 ESCC 细胞的增殖、迁移、侵袭,并诱导细胞周期停滞在 G0/G1 期。circ_0023984 通过调节 miR-1294 的表达影响 ESCC 的进展。miR-1294 的靶基因与细胞周期阻滞和 PI3K-Akt 信号通路有关。circ_0023984 通过抑制 miR-1294 来上调 p-Akt 和 c-Myc 的表达。circ_0023984 通过抑制 miR-1294 并激活 PI3K/Akt/c-myc 通路促进 ESCC 细胞的恶性生物学行为。

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