Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300000, P.R. China.
Department of Obstetrics and Gynecology, Affiliated Hospital of North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11876. Epub 2021 Feb 4.
MicroRNA‑199a‑3p (miR‑199a‑3p) is aberrantly expressed in various types of cancer where it exhibits a tumor suppressive role. However, the biological role of miR‑199a‑3p in ovarian cancer (OC) remains unclear. The present study aimed to investigate whether miR‑199a‑3p was a tumor suppressor in OC and to identify the possible mechanisms. It was found that miR‑199a‑3p expression was significantly downregulated in the tumor tissues and blood samples of patients with OC, as well as in three OC cell lines. In addition, its low expression was closely associated with International Federation of Gynecology and Obstetrics disease stage, histological grade and lymph node metastasis. It was demonstrated that overexpression of miR‑199a‑3p inhibited the viability and promoted apoptosis of OV90 and SKOV‑3 cells. In addition, Yes‑associated protein 1 (YAP1), a well‑known oncogene, was identified as a direct target of miR‑199a‑3p in OC cells. Additionally, it was observed that YAP1 was significantly increased and inversely correlated with miR‑199a‑3p expression in OC tissues. Notably, YAP1 overexpression abrogated the tumor suppressive effects of miR‑199a‑3p . Collectively, the present results indicated that miR‑199a‑3p suppressed viability in OC cells, at least partly via inhibiting the YAP1 oncogene, suggesting that miR‑199a‑3p may act as a biomarker and therapeutic target for patients with OC.
微小 RNA-199a-3p(miR-199a-3p)在各种类型的癌症中表达异常,在这些癌症中发挥肿瘤抑制作用。然而,miR-199a-3p 在卵巢癌(OC)中的生物学作用尚不清楚。本研究旨在探讨 miR-199a-3p 是否在 OC 中起肿瘤抑制作用,并确定可能的机制。结果发现,miR-199a-3p 在 OC 患者的肿瘤组织和血液样本以及三种 OC 细胞系中表达明显下调。此外,其低表达与国际妇产科联合会疾病分期、组织学分级和淋巴结转移密切相关。研究表明,miR-199a-3p 的过表达抑制了 OV90 和 SKOV-3 细胞的活力并促进了细胞凋亡。此外,Yes 相关蛋白 1(YAP1),一种众所周知的癌基因,被鉴定为 OC 细胞中 miR-199a-3p 的直接靶标。此外,还观察到 YAP1 在 OC 组织中显著增加且与 miR-199a-3p 表达呈负相关。值得注意的是,YAP1 的过表达消除了 miR-199a-3p 的肿瘤抑制作用。综上所述,本研究结果表明,miR-199a-3p 通过抑制 YAP1 癌基因抑制 OC 细胞的活力,至少部分发挥作用,提示 miR-199a-3p 可能作为 OC 患者的生物标志物和治疗靶点。