Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
Department of Pathology, Heilongjiang Province Land Reclamation Headquarter General Hospital, Harbin, China.
Bioengineered. 2021 Dec;12(1):7859-7871. doi: 10.1080/21655979.2021.1967009.
Previous studies have explored the association between protein-coding genes and microRNAs (miRNAs) in lung adenocarcinoma (LUAD). However, the influence of the miR-199a-3p/anterior gradient 2 (AGR2) axis in LUAD has not yet been fully explored. Therefore, this study aimed to examine the underlying roles of AGR2 and miR-199a-3p in the development of LUAD. The expression levels of miR-199a-3p and AGR2 in LUAD tissues and cells were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A luciferase assay was also performed to identify the interaction between AGR2 and miR-199a-3p. Moreover, the cell counting kit 8 (CCK-8), 5'-bromo-2'-deoxyuridine (BrdU), and adhesion assays were used along with flow cytometry to verify the malignancy of LUAD in vitro, while a xenograft tumor assay was performed to confirm the tumor growth in vitro. The findings showed a decrease in the expression of miR-199a-3p in LUAD. Additionally, miR-199a-3p overexpression inhibited the growth of LUAD cells in vitro and in vivo, while elevating the apoptosis rate of the cells. AGR2 knockdown had the same effect in the cells as that of miR-199a-3p overexpression. It was also found that miR-199a-3p directly targeted AGR2 in LUAD cells to suppress tumorigenesis. In conclusion, this study suggests that miR-199a-3p plays an anti-tumorigenic role in LUAD by targeting AGR2. Moreover, our study provides insights into the development of novel therapeutic targets for the treatment of LUAD.
先前的研究已经探讨了肺腺癌(LUAD)中蛋白质编码基因与 microRNAs(miRNAs)之间的关联。然而,miR-199a-3p/前梯度 2(AGR2)轴在 LUAD 中的影响尚未得到充分探索。因此,本研究旨在研究 AGR2 和 miR-199a-3p 在 LUAD 发展中的潜在作用。通过定量逆转录聚合酶链反应(qRT-PCR)检测 LUAD 组织和细胞中 miR-199a-3p 和 AGR2 的表达水平。还进行了荧光素酶测定以鉴定 AGR2 和 miR-199a-3p 之间的相互作用。此外,使用细胞计数试剂盒 8(CCK-8)、5'-溴-2'-脱氧尿苷(BrdU)和粘附测定以及流式细胞术验证 LUAD 在体外的恶性程度,而进行异种移植肿瘤测定以确认体外肿瘤生长。研究结果表明,miR-199a-3p 在 LUAD 中的表达降低。此外,miR-199a-3p 的过表达抑制了 LUAD 细胞在体外和体内的生长,同时提高了细胞的凋亡率。AGR2 敲低在细胞中的作用与 miR-199a-3p 的过表达相同。还发现 miR-199a-3p 在 LUAD 细胞中直接靶向 AGR2 以抑制肿瘤发生。总之,本研究表明 miR-199a-3p 通过靶向 AGR2 在 LUAD 中发挥抗肿瘤作用。此外,我们的研究为 LUAD 治疗的新型治疗靶点的开发提供了思路。