Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4113-4122. doi: 10.26355/eurrev_202004_20990.
Ovarian cancer (OC) is a deathful malignant tumor in women worldwide, and its poor prognosis mainly results from metastasis. Recently, microRNA (miRNA/miR) has been found to exert crucial functions in the progression of multiple tumors by affecting expressions of their targets. However, the biological roles and the potential mechanism of miR-489 in OC need further elucidation.
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to confirm the miR-489 expressions in OC tissue samples and cell lines. The functions of miR-489 were analyzed by performing functional assays, such as MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays. The downstream target of miR-489 was confirmed by TargetScan and luciferase reporter assay. Western blot was conducted to detect the expression of indicators associated with the down-stream signaling pathway.
MiR-489 was prominently downregulated in OC tissues and cells, and the decreased miR-489 expression was related to malignant clinicopathologic features and poor prognosis of OC patients. Functional assays demonstrated that miR-489 could suppress OC cell viability, invasion, and migration. X-linked inhibitor of apoptosis protein (XIAP) was identified as a target of miR-489 and partially regulated the functions of miR-489 in OC. Moreover, we found that miR-489 inhibits OC progression via regulating phosphatidyl-inositol 3-kinase/protein kinase B pathway (PI3K/AKT) and epithelial-to-mesenchymal transition (EMT).
Our results demonstrated that miR-489 inhibited OC development by directly binding to XIAP and regulating PI3K/Akt and EMT signal pathways, and miR-489 might serve as a promising biomarker for OC treatment in the future.
卵巢癌（OC）是全球女性致死性恶性肿瘤，其预后不良主要归因于转移。最近，微 RNA（miRNA/miR）被发现通过影响其靶基因的表达，在多种肿瘤的进展中发挥关键作用。然而，miR-489 在 OC 中的生物学功能和潜在机制仍需进一步阐明。
采用实时定量聚合酶链反应（qRT-PCR）验证 OC 组织样本和细胞系中 miR-489 的表达。通过 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）检测、transwell 检测等功能实验分析 miR-489 的功能。通过 TargetScan 和荧光素酶报告基因实验验证 miR-489 的下游靶基因。Western blot 检测与下游信号通路相关的指标表达。
miR-489 在 OC 组织和细胞中显著下调，miR-489 表达降低与 OC 患者恶性临床病理特征和不良预后相关。功能实验表明，miR-489 可抑制 OC 细胞活力、侵袭和迁移。X 连锁凋亡抑制蛋白（XIAP）被鉴定为 miR-489 的靶基因，并部分调控 miR-489 在 OC 中的功能。此外，我们发现 miR-489 通过调节磷脂酰肌醇 3-激酶/蛋白激酶 B 通路（PI3K/AKT）和上皮间质转化（EMT）抑制 OC 进展。
本研究结果表明，miR-489 通过直接结合 XIAP 并调控 PI3K/Akt 和 EMT 信号通路抑制 OC 的发展，miR-489 可能成为未来 OC 治疗的有前途的标志物。
