School of Medicine, Yunnan University, Kunming, Yunnan 650091, P.R. China.
Department of Gynecology, Yunnan Tumor Hospital & The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China.
Mol Med Rep. 2020 Oct;22(4):3429-3439. doi: 10.3892/mmr.2020.11428. Epub 2020 Aug 11.
Previous studies have reported that long non‑coding RNAs (lncRNAs) have a significant role in the metastasis of tumors, including ovarian cancer (OC). The aim of the present study was to demonstrate the function and working mechanism of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in OC. The expressions of NEAT1 in OC were measured by reverse transcription‑quantitativePCR (RT‑qPCR). The effects of NEAT1 on cell proliferation, invasion, migration and epithelial‑mesenchymal transition (EMT) were detected by Cell Counting Kit‑8, transwell and wound healing assays, and western blotting. Dual‑luciferase reporter assays were performed to confirm the correlated between NEAT and miR‑1321, miR‑1321 and TJP3. The effect of NEAT1 on miR‑1321 and TJP3 was confirmed by RT‑qPCR and western blotting. Elevated expression of NEAT1 was observed in OC cell lines, and NEAT1 expression was found to be positively related to the expression of tight junction protein 3 (TJP3), which is important in cancer development. Moreover, the present results indicated that NEAT1 and TJP3 expression levels were negatively correlated with microRNA (miR)‑1321 expression in OC. Knockdown of NEAT1 attenuated the migration and invasion of OC cells, as well as increased miR‑1321 expression and in turn led to the reduction of TJP3. Thus, the present study demonstrated that NEAT1 regulates TJP3 expression by sponging miR‑1321 and enhances the epithelial‑mesenchymal transition, invasion and migration of OC cells. Overall, the present study identified the function and mechanism of NEAT1 in OC, suggesting that NEAT1 may be a promising therapeutic target for OC metastasis.
先前的研究已经表明,长链非编码 RNA(lncRNA)在肿瘤转移中具有重要作用,包括卵巢癌(OC)。本研究旨在阐明 lncRNA 核富集丰富转录物 1(NEAT1)在 OC 中的功能和作用机制。通过逆转录定量 PCR(RT-qPCR)测量 OC 中 NEAT1 的表达。通过细胞计数试剂盒-8、Transwell 和划痕愈合试验以及 Western blot 检测 NEAT1 对细胞增殖、侵袭、迁移和上皮-间充质转化(EMT)的影响。双荧光素酶报告基因检测用于证实 NEAT 与 miR-1321、miR-1321 与 TJP3 之间的相关性。通过 RT-qPCR 和 Western blot 证实了 NEAT1 对 miR-1321 和 TJP3 的影响。结果表明 OC 细胞系中 NEAT1 的表达升高,并且 NEAT1 的表达与紧密连接蛋白 3(TJP3)的表达呈正相关,TJP3 在癌症发展中具有重要作用。此外,本研究结果表明,OC 中 NEAT1 和 TJP3 的表达水平与 microRNA(miR)-1321 的表达呈负相关。敲低 NEAT1 可减弱 OC 细胞的迁移和侵袭,并增加 miR-1321 的表达,从而降低 TJP3 的表达。因此,本研究表明 NEAT1 通过海绵吸附 miR-1321 来调节 TJP3 的表达,从而增强 OC 细胞的上皮-间充质转化、侵袭和迁移。总之,本研究确定了 NEAT1 在 OC 中的功能和机制,表明 NEAT1 可能是 OC 转移的有前途的治疗靶点。