Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang.
Department of Nuclear Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang.
Eur J Histochem. 2021 Nov 16;65(4):3300. doi: 10.4081/ejh.2021.3300.
The long non-coding FGD5-AS1 (LncFGD5-AS1) has been reported to be a novel carcinogenic gene and participant in regulating tumor progression by sponging microRNAs (miRNAs). However, the pattern of expression and the biological role of FGD5-AS1 in hepatocellular carcinoma (HCC) remains largely unknown. The expression level of FGD5-AS1 in tumor tissues and cell lines was measured by RT-qPCR. CCK-8, EdU, flow cytometry, wound healing, and transwell chamber assays were performed to investigate the role of FGD5-AS1 in cell proliferation, apoptosis, migration, and invasion in HCC. Dual luciferase reporter, and RNA pull-down assays were performed to identify the regulatory interactions among FGD5-AS1, miR-873-5p and GTP-binding protein 4 (GTPBP4). We found that the expression of FGD5-AS1 was upregulated in HCC tissues and cell lines. Moreover, the knockdown of FGD5-AS1 suppressed cell proliferation, migration and invasion, and induced apoptosis in HCC cells. Further studies demonstrated that FGD5-AS1 could function as a competitive RNA by sponging miR-873-5p in HCC cells. Moreover, GTPBP4 was identified as direct downstream target of miR-873-5p in HCC cells and FGD5-AS1mediated the effects of GTPBP4 by competitively binding with miR-873-5p. Taken together, this study demonstrated the regulatory role of FGD5-AS1 in the progression of HCC and identified the miR-873-5p/GTPBP4 axis as the direct downstream pathway. It represents a promising novel therapeutic strategy for HCC patients.
长链非编码 FGD5-AS1（LncFGD5-AS1）已被报道为一种新型致癌基因，并通过海绵 microRNAs（miRNAs）参与调节肿瘤进展。然而，FGD5-AS1 在肝细胞癌（HCC）中的表达模式和生物学作用在很大程度上仍不清楚。通过 RT-qPCR 测量肿瘤组织和细胞系中 FGD5-AS1 的表达水平。通过 CCK-8、EdU、流式细胞术、划痕愈合和 Transwell 室测定来研究 FGD5-AS1 在 HCC 细胞增殖、凋亡、迁移和侵袭中的作用。双荧光素酶报告和 RNA 下拉测定用于鉴定 FGD5-AS1、miR-873-5p 和 GTP 结合蛋白 4（GTPBP4）之间的调节相互作用。我们发现 FGD5-AS1 的表达在 HCC 组织和细胞系中上调。此外，FGD5-AS1 的敲低抑制 HCC 细胞的增殖、迁移和侵袭，并诱导细胞凋亡。进一步的研究表明，FGD5-AS1 可以作为 HCC 细胞中的竞争性 RNA 通过海绵 miR-873-5p 发挥作用。此外，GTPBP4 被鉴定为 HCC 细胞中 miR-873-5p 的直接下游靶标，并且 FGD5-AS1 通过与 miR-873-5p 竞争结合来介导 GTPBP4 的作用。总之，这项研究证明了 FGD5-AS1 在 HCC 进展中的调节作用，并确定了 miR-873-5p/GTPBP4 轴作为直接下游途径。它为 HCC 患者提供了一种有前途的新型治疗策略。
