ANGPTL4 是 hsa-miR-133a-3p 的直接靶标，可加速肺腺癌的脂质代谢、增殖和侵袭。
ANGPTL4, a direct target of hsa-miR-133a-3p, accelerates lung adenocarcinoma lipid metabolism, proliferation and invasion.
机构信息
Department of Thoracic Surgery, The First People’s Hospital of Changde City, Changde, Hunan, China.
Department of Assisted Reproductive Centre, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.
出版信息
Aging (Albany NY). 2023 Dec 29;16(9):8348-8360. doi: 10.18632/aging.205313.
BACKGROUND
Globally, lung adenocarcinoma (LUAD) is the most common type of lung cancer. The secreted protein angiopoietin-like 4 (ANGPTL4) has been implicated in a number of physiological and pathological processes, including angiogenesis and lipid metabolism. But the role of ANGPTL4 in LUAD remains unknown.
METHODS
The expression of ANGPTL4 and miR-133a-3p was confirmed by public database analysis. Xenograft model, MTT, Clone formation and EdU analysis were used to confirm the effects of miR-133a-3p/ANGPTL4 on LUAD cell proliferation and growth. Wound healing and Transwell analysis were used to elucidate the role of miR-133a-3p/ANGPTL4 in LUAD cell migration and invasion. Oil red O staining was used to confirm ANGPTL4 in LUAD lipids production. Dual-luciferase reporter gene analysis was used to demonstrate miR-133a-3p could directly bind ANGPTL4 3'-UTR. WB and PCR were used to confirm the protein expression of ANGPTL4.
RESULTS
ANGPTL4 was significantly increased in LUAD samples, which could promote LUAD cell proliferation, migration, invasion, growth and lipid production. miR-133a-3p could directly bind to ANGPTL4 mRNA, and repress the expression ANGPTL4, resulting in suppressing LUAD proliferation and metastasis.
CONCLUSION
In conclusion, miR-133a-3p/ANGPTL4 axis might be a potential biomarker and therapeutic target for LUAD patients.
背景
在全球范围内，肺腺癌（LUAD）是最常见的肺癌类型。分泌蛋白血管生成素样 4（ANGPTL4）参与了许多生理和病理过程，包括血管生成和脂代谢。但是 ANGPTL4 在 LUAD 中的作用尚不清楚。
方法
通过公共数据库分析证实了 ANGPTL4 和 miR-133a-3p 的表达。异种移植模型、MTT、克隆形成和 EdU 分析用于证实 miR-133a-3p/ANGPTL4 对 LUAD 细胞增殖和生长的影响。划痕愈合和 Transwell 分析用于阐明 miR-133a-3p/ANGPTL4 在 LUAD 细胞迁移和侵袭中的作用。油红 O 染色用于证实 ANGPTL4 在 LUAD 脂质产生中的作用。双荧光素酶报告基因分析用于证明 miR-133a-3p 可以直接结合 ANGPTL4 3'-UTR。WB 和 PCR 用于证实 ANGPTL4 的蛋白表达。
结果
ANGPTL4 在 LUAD 样本中显著增加，可促进 LUAD 细胞增殖、迁移、侵袭、生长和脂质生成。miR-133a-3p 可以直接结合 ANGPTL4 mRNA，抑制 ANGPTL4 的表达，从而抑制 LUAD 的增殖和转移。
结论
总之，miR-133a-3p/ANGPTL4 轴可能是 LUAD 患者的潜在生物标志物和治疗靶点。
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