Department of Surgery, Yinchuan Maternal and Child Health Hospital, Yinchuan, Ningxia 750001, P.R. China.
Department of Surgical Oncology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Mol Med Rep. 2021 Jun;23(6). doi: 10.3892/mmr.2021.12099. Epub 2021 Apr 21.
Breast cancer is the second most prevalent cancer in women worldwide. Long non‑coding RNAs (lncRNAs) have been identified as important regulators of tumorigenesis and tumor metastasis. lncRNA FGD5‑AS1 has been previously reported as a carcinogenic gene, however its role in breast cancer has yet to be investigated. The present study aimed to understand the function of lncRNA FGD5‑AS1 in breast cancer and examine the underlying molecular mechanisms. Sample tissues for downstream gene expression profiling were collected from patients with breast cancer (n=23). The effect of FGD5‑AS1 overexpression on cell viability, invasion and migration has been studied in breast cancer cells (MDA‑MB‑231). Changes in glycolysis were monitored by comparing glucose consumption, lactate production and ATP levels. Using StarBase and TargetScan databases a putative interaction between FGD5‑AS1, miR‑195‑5p and SNF1‑like kinase 2 (NUAK2) was predicted . Expression levels of FGD5‑AS1, has‑miR‑195‑5p and NUAK2 were validated by reverse transcription‑quantitative PCR and interactions were validated using dual‑luciferase reporter assays and RNA pull‑down. High expression of lncRNA FGD5‑AS1 was detected in breast cancer tissue samples and disease model cell lines. Silencing of FGD5‑AS1 led to decreased cell proliferation, migration and invasion. It was identified that at a molecular level FGD5‑AS1 serves as a sponge of miR‑195‑5p and alters the expression of its downstream target gene NUAK2. In breast cancer lncRNA FGD5‑AS1 serve a key role in glycolysis and tumor progression via the miR‑195‑5p/NUAK2 axis. The findings of the present study indicated FGD5‑AS1 as a candidate target for intervention in patients with breast cancer.
乳腺癌是全球女性中第二大常见癌症。长链非编码 RNA（lncRNA）已被确定为肿瘤发生和肿瘤转移的重要调节剂。lncRNA FGD5-AS1 先前被报道为致癌基因，但其在乳腺癌中的作用尚未得到研究。本研究旨在了解 lncRNA FGD5-AS1 在乳腺癌中的功能，并探讨其潜在的分子机制。从乳腺癌患者（n=23）中收集用于下游基因表达谱分析的组织样本。在乳腺癌细胞（MDA-MB-231）中研究了 FGD5-AS1 过表达对细胞活力、侵袭和迁移的影响。通过比较葡萄糖消耗、乳酸生成和 ATP 水平来监测糖酵解的变化。使用 StarBase 和 TargetScan 数据库预测了 FGD5-AS1、miR-195-5p 和 SNF1 样激酶 2（NUAK2）之间的假定相互作用。通过逆转录-定量 PCR 验证了 FGD5-AS1、has-miR-195-5p 和 NUAK2 的表达水平，并通过双荧光素酶报告基因检测和 RNA 下拉实验验证了相互作用。在乳腺癌组织样本和疾病模型细胞系中检测到 lncRNA FGD5-AS1 的高表达。FGD5-AS1 的沉默导致细胞增殖、迁移和侵袭减少。研究表明，在分子水平上，FGD5-AS1 作为 miR-195-5p 的海绵，并改变其下游靶基因 NUAK2 的表达。在乳腺癌中，lncRNA FGD5-AS1 通过 miR-195-5p/NUAK2 轴在糖酵解和肿瘤进展中发挥关键作用。本研究的结果表明，FGD5-AS1 是乳腺癌患者干预的候选靶点。
