Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602‑8566, Japan.
Int J Mol Med. 2022 Jun;49(6). doi: 10.3892/ijmm.2022.5139. Epub 2022 Apr 29.
As liver cancer (LC) is the sixth most commonly diagnosed malignancy, it is necessary to elucidate the molecular mechanisms responsible for LC progression. MicroRNAs (miRNAs/miRs) play crucial roles in tumor progression by regulating target gene expression. The present study assessed miRNA‑4730 expression and function in LC. The effects of miR‑4730 overexpression were examined in LC cell lines, and the target genes of miR‑4730 were evaluated using microarray analysis and TargetScan data. In addition, the association between miR‑4730 expression in tissue samples and the prognosis of 70 patients with LC was evaluated. miR‑4730 expression was suppressed in LC tissues and cell lines. miR‑4730 overexpression suppressed cell proliferation and cell cycle progression and promoted apoptosis. High mobility group A1 (HMGA1) was revealed as the direct target of miR‑4730 using luciferase reporter assay, and the inhibition of downstream integrin‑linked kinase (ILK) expression and Akt or glycogen synthase kinase 3β (GSK3β) phosphorylation was confirmed. The lower expression of miR‑4730 in tissue samples was significantly associated with a worse recurrence‑free survival of patients with LC. On the whole, miR‑4730 suppressed tumor progression by directly targeting HMGA1 and inhibiting the ILK/Akt/GSK3β pathway. miR‑4730 thus has potential for use as a prognostic marker and may prove to be a therapeutic target for miRNA‑based therapies.
由于肝癌 (LC) 是第六种最常见的恶性肿瘤,因此有必要阐明导致 LC 进展的分子机制。MicroRNAs (miRNAs/miRs) 通过调节靶基因表达在肿瘤进展中发挥关键作用。本研究评估了 miRNA-4730 在 LC 中的表达和功能。在 LC 细胞系中检查了 miR-4730 过表达的影响,并使用微阵列分析和 TargetScan 数据评估了 miR-4730 的靶基因。此外,还评估了组织样本中 miR-4730 表达与 70 例 LC 患者预后之间的相关性。miR-4730 在 LC 组织和细胞系中表达受到抑制。miR-4730 过表达抑制细胞增殖和细胞周期进程,促进细胞凋亡。高迁移率族蛋白 A1 (HMGA1) 通过荧光素酶报告基因检测被揭示为 miR-4730 的直接靶标,并且证实了下游整合素连接激酶 (ILK) 表达和 Akt 或糖原合成酶激酶 3β (GSK3β) 磷酸化的抑制。组织样本中 miR-4730 的低表达与 LC 患者无复发生存率较差显著相关。总的来说,miR-4730 通过直接靶向 HMGA1 并抑制 ILK/Akt/GSK3β 通路抑制肿瘤进展。因此,miR-4730 具有作为预后标志物的潜力,并可能被证明是 miRNA 为基础的治疗的治疗靶点。