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环状 RNA 0008068 通过 microRNA-153-3p/酰基甘油激酶 (AGK) 轴促进口腔鳞状细胞癌的发展。

Circ_0008068 facilitates the oral squamous cell carcinoma development by microRNA-153-3p/acylgycerol kinase (AGK) axis.

机构信息

Department of Prosthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Department of Oral and Maxillofacial Surgery, Henan Provincial Stomatological Hospital, Zhengzhou, Henan, China.

出版信息

Bioengineered. 2022 May;13(5):13055-13069. doi: 10.1080/21655979.2022.2074106.

Abstract

Oral squamous cell carcinoma (OSCC) is a common cancer with high recurrence, metastasis rates and poor prognosis. Circular RNAs (circRNAs) take part in regulating OSCC. Herein, we examined the role of circ_0008068 in OSCC. The circ_0008068, Katanin p60 ATPase-containing subunit A-like 1 (KATNAL1) mRNA, microRNA-153-3p (miR-153-3p) and acylgycerol kinase (AGK) contents were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Moreover, in vitro and in vivo assays were conducted to scrutinize the effects of circ_0008068 on OSCC. Additionally, the contact between miR-153-3p and circ_0008068 or AGK was assessed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Thereafter, we found that the appearance of circ_0008068 and AGK was increased, and miR-153-3p content was diminished in OSCC. Circ_0008068 lack subdued cell proliferation, migration, invasion, tube formation and glycolysis metabolism, but stimulated cell apoptosis in OSCC. In addition, circ_0008068 bound to miR-153-3p to modulate the expression of its target AGK. Besides, miR-153-3p was validated to act as a tumor suppressor in OSCC tumorigenesis by suppressing AGK. Additionally, circ_0008068 knockdown also attenuated tumor growth in nude mice. In all, circ_0008068 expedited the growth of OSCC by miR-153-3p/AGK axis. OSCC: Oral squamous cell carcinoma; AGK: Acylgycerol kinase; CircRNA: Circular RNA; KATNAL1: Katanin p60 ATPase-containing subunit A-like 1; qRT-PCR: Quantitative real-time polymerase chain reaction; miRNAs/miRs: MicroRNAs; RIP: RNA immunoprecipitation; 3'UTR3': -untranslated region; HK2: Hexokinase 2; LDHA Lactate dehydrogenase A; IHC: Immunohistochemistry; CCK8: Cell counting kit-8; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.

摘要

口腔鳞状细胞癌(OSCC)是一种常见的癌症,具有高复发率、转移率和预后不良的特点。环状 RNA(circRNA)参与调节 OSCC。在此,我们研究了 circ_0008068 在 OSCC 中的作用。通过定量实时聚合酶链反应(qRT-PCR)和 Western blot 检测 circ_0008068、Katanin p60 ATPase 含有亚基 A 样 1(KATNAL1)mRNA、微小 RNA-153-3p(miR-153-3p)和酰基甘油激酶(AGK)的含量。此外,还进行了体外和体内实验来研究 circ_0008068 对 OSCC 的影响。此外,通过双荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)实验评估了 miR-153-3p 与 circ_0008068 或 AGK 之间的相互作用。随后,我们发现 circ_0008068 和 AGK 的表达增加,而 miR-153-3p 的含量在 OSCC 中减少。circ_0008068 缺失可抑制 OSCC 细胞的增殖、迁移、侵袭、管形成和糖酵解代谢,但促进细胞凋亡。此外,circ_0008068 与 miR-153-3p 结合,调节其靶基因 AGK 的表达。此外,miR-153-3p 通过抑制 AGK 在 OSCC 肿瘤发生中发挥肿瘤抑制作用。此外,circ_0008068 敲低也可抑制裸鼠肿瘤生长。总之,circ_0008068 通过 miR-153-3p/AGK 轴促进 OSCC 的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18d8/9275858/b898dc7a59eb/KBIE_A_2074106_UF0001_OC.jpg

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