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LINC-PINT 通过靶向 miR-374a-5p 抑制卵巢癌细胞的增殖、迁移和侵袭。

LINC-PINT suppresses tumour cell proliferation, migration and invasion through targeting miR-374a-5p in ovarian cancer.

机构信息

Department of Pathology, Heze Municipal Hospital, Heze, China.

Department of Oncology, Heze Municipal Hospital, Heze, China.

出版信息

Cell Biochem Funct. 2020 Dec;38(8):1089-1099. doi: 10.1002/cbf.3565. Epub 2020 Jul 7.

Abstract

LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of ovarian cancer (OC). LINC-PINT expression level in different FIGO stages of OC and its adjacent tissues, normal HOSE and OC cell lines (A2780, SKOV3, OVCAR3 and HO-8910) was determined by qRT-PCR. Survival analysis on LINC-PINT and OC patients was conducted by Kaplan-Meier. CCK-8, flow cytometry, wound-healing, Transwell assays and western blot were performed to detect the effects of LINC-PINT on proliferation, apoptosis, migration, invasion and EMT process in OC cells. Target gene of LINC-PINT was predicted by Starbase and verified by dual-luciferase reporter assay. The expression of miR-374a-5p in normal and OC tissues, LINC-PINT- or siLINC-PINT-modified OC cells was determined. Moreover, rescue assay was carried out to confirm whether LINC-PINT contributes to the development of OC cells through targeting miR-374a-5p. Low expression of LINC-PINT was observed in OC tissues and cells, noticeably, LINC-PINT expression was even lower in OC tissues with higher FIGO stage. Increased LINC-PINT expression significantly inhibited cell proliferation, promoted apoptosis and suppressed migration, invasion and EMT process, while silencing of LINC-PINT caused the opposite results. Moreover, LINC-PINT sponged miR-374a-5p and overexpressed miR-374a-5p attenuated the effect of up-regulated LINC-PINT on cell viability, migration, invasion and apoptosis. LINC-PINT acts as a tumour suppressor, as it could inhibit cell proliferation, migration, invasion and EMT process, and promote cell apoptosis through down-regulating miR-374a-5p. SIGNIFICANCE OF THE STUDY: Ovarian cancer (OC), which is a frequently diagnosed tumour in female reproductive organs, has a high incidence rate behind cervical cancer and endometrial cancer. LncRNA LINC-PINT acts as an important regulator in the development of many cancers. The current study aimed to explore the role of LINC-PINT in the progression of ovarian cancer (OC) and found that LINC-PINT inhibited cell proliferation, migration invasion and EMT process of OC cell via regulating miR-374a-5p; it might be a potential target for OC treatment.

摘要

LncRNA LINC-PINT 在许多癌症的发展中起着重要的调节作用。本研究旨在探讨 LINC-PINT 在卵巢癌(OC)进展中的作用。通过 qRT-PCR 测定不同 FIGO 分期 OC 及其相邻组织、正常 HOSE 和 OC 细胞系(A2780、SKOV3、OVCAR3 和 HO-8910)中 LINC-PINT 的表达水平。通过 Kaplan-Meier 对 LINC-PINT 和 OC 患者进行生存分析。通过 CCK-8、流式细胞术、划痕愈合、Transwell 测定和 Western blot 检测 LINC-PINT 对 OC 细胞增殖、凋亡、迁移、侵袭和 EMT 过程的影响。通过 Starbase 预测 LINC-PINT 的靶基因,并通过双荧光素酶报告实验验证。测定正常和 OC 组织、LINC-PINT 或 siLINC-PINT 修饰的 OC 细胞中 miR-374a-5p 的表达。此外,进行挽救实验以确认 LINC-PINT 是否通过靶向 miR-374a-5p 促进 OC 细胞的发展。在 OC 组织和细胞中观察到 LINC-PINT 的低表达,值得注意的是,在 FIGO 分期较高的 OC 组织中,LINC-PINT 的表达甚至更低。增加 LINC-PINT 的表达显著抑制细胞增殖,促进凋亡,并抑制迁移、侵袭和 EMT 过程,而沉默 LINC-PINT 则产生相反的结果。此外,LINC-PINT 海绵吸附 miR-374a-5p,过表达 miR-374a-5p 减弱上调 LINC-PINT 对细胞活力、迁移、侵袭和凋亡的影响。LINC-PINT 作为一种肿瘤抑制因子,通过下调 miR-374a-5p 抑制细胞增殖、迁移、侵袭和 EMT 过程,促进细胞凋亡。

这项研究的意义在于

卵巢癌(OC)是女性生殖器官中常见的肿瘤之一,其发病率仅次于宫颈癌和子宫内膜癌。LncRNA LINC-PINT 在许多癌症的发展中起着重要的调节作用。本研究旨在探讨 LINC-PINT 在卵巢癌(OC)进展中的作用,发现 LINC-PINT 通过调节 miR-374a-5p 抑制 OC 细胞的增殖、迁移、侵袭和 EMT 过程;它可能是 OC 治疗的一个潜在靶点。

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