miR-643 通过靶向 TXNDC9 抑制细胞增殖和侵袭，在胃癌中发挥潜在的肿瘤抑制作用。
MiR-643 Functions as a Potential Tumor Suppressor in Gastric Cancer by Inhibiting Cell Proliferation and Invasion Targeting TXNDC9.
机构信息
Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
出版信息
Ann Clin Lab Sci. 2021 Jul;51(4):494-502.
OBJECTIVE
Gastric cancer is one of the most common gastrointestinal malignancies. miRNAs (microRNAs) have been reported to play a pivotal role in the tumorigenesis of gastric cancer. However, the role of miR-643 in gastric cancer is not fully understood.
METHODS
The expression of miR-643 in gastric cancer cell lines was detected by qRT-PCR (quantitative reverse transcription PCR). Cell viability, apoptosis, migration, and invasion were assessed using the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and wound scratch and Transwell assays, respectively. The target gene of miR-643 was predicted by bioinformatics analysis and validated using luciferase reporter assay.
RESULTS
The expression level of miR-643 in gastric cancer cell lines was lower than in the normal gastric epithelium cell line (GES-1). Overexpression of miR-643 inhibited cell viability and colony formation but promoted cell apoptosis in gastric cancer. Transwell invasion assay and scratch assay evidenced that miR-643 overexpression inhibited gastric cancer cell migration and invasion. Bioinformatics analysis revealed that miR-643 could directly target TXNDC9 (Thioredoxin domain containing 9), and luciferase reporter assay validated this result. Further analysis showed that miR-643 mimics caused a significant reduction of TXNDC9 in gastric cancer cells. Moreover, TXNDC9 overexpression reversed the effects of miR-643 mimics on gastric cancer cell viability, invasion, and migration.
CONCLUSION
miR-643 functions as a potential tumor suppressor in gastric cancer by inhibiting cell viability, colony formation, migration, and invasion via targeting TXNDC9, which provides a novel target for the diagnostic treatment of gastric cancer.
目的
胃癌是最常见的胃肠道恶性肿瘤之一。miRNAs（microRNAs）已被报道在胃癌的发生发展中发挥关键作用。然而，miR-643 在胃癌中的作用尚不完全清楚。
方法
通过 qRT-PCR（定量逆转录 PCR）检测胃癌细胞系中 miR-643 的表达。使用细胞计数试剂盒-8（CCK-8）、集落形成、流式细胞术、划痕和 Transwell 测定分别评估细胞活力、凋亡、迁移和侵袭。通过生物信息学分析预测 miR-643 的靶基因，并通过荧光素酶报告基因实验进行验证。
结果
胃癌细胞系中 miR-643 的表达水平低于正常胃上皮细胞系（GES-1）。miR-643 的过表达抑制胃癌细胞活力和集落形成，但促进细胞凋亡。Transwell 侵袭实验和划痕实验表明 miR-643 过表达抑制胃癌细胞迁移和侵袭。生物信息学分析表明，miR-643 可以直接靶向 TXNDC9（硫氧还蛋白结构域包含 9），荧光素酶报告基因实验验证了这一结果。进一步分析表明，miR-643 模拟物导致胃癌细胞中 TXNDC9 的显著减少。此外，TXNDC9 的过表达逆转了 miR-643 模拟物对胃癌细胞活力、侵袭和迁移的影响。
结论
miR-643 通过靶向 TXNDC9 抑制胃癌细胞活力、集落形成、迁移和侵袭，作为胃癌中的潜在肿瘤抑制因子发挥作用，为胃癌的诊断和治疗提供了新的靶点。
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