长链非编码 RNA PVT1 通过 miR-128/ZEB1 轴促进肿瘤进展，并预测食管癌的预后不良。

Long noncoding RNA PVT1 promotes tumour progression via the miR-128/ZEB1 axis and predicts poor prognosis in esophageal cancer.

机构信息

Department of Digestive, Shijiazhuang People's Hospital, Shijiazhuang 050011, China.

出版信息

Clin Res Hepatol Gastroenterol. 2021 Jul;45(4):101701. doi: 10.1016/j.clinre.2021.101701. Epub 2021 Apr 10.

DOI:10.1016/j.clinre.2021.101701

PMID:33848670

Abstract

PURPOSE

To confirm the value of PVT1 as a prognostic marker both in tumour tissue and serum of patients with esophageal cancer and clarify the mechanism.

METHODS

This study analyzed data obtained from 76 patients who were surgically treated from January 1, 2015, to December 31, 2016, and received a pathological diagnosis of ESCC. PVT1 levels in tumour tissue and serum were detected by qRT-PCR. Patient data were extracted from medical records, and follow-up evaluations were performed. The roles of PVT1 in proliferation, migration and invasion were by CCK-8 and Transwell in stable knockdown PVT1 cell lines. Signal pathways PVT1 promotes esophageal cancer were detected by qRT-PCR and western blot.

RESULTS

PVT1 was overexpression in esophageal cancer tissues and high levels of PVT1 were correlated with lymphatic metastasis, high TNM stage and postoperative metastasis. High levels of PVT1 in tissues were correlated with worse metastasis-free survival (MFS) (HR: 2.578, 95% CI: 1.369-4.853). High level of PVT1 in serum was correlated with postoperative metastasis. High levels of PVT1 in serum were correlated with worse overall survival (OS) (HR: 2.124, 95% CI: 1.078-4.186) and worse MFS (HR: 2.786, 95% CI: 1.557-4.985). Knockdown of PVT1 decreased the cell proliferation, migration and invasion abilities of esophageal cancer cell lines. The expression of ZEB1 was significantly downregulated, and the expression of E-cadherin was increased by the knockdown of PVT1. Knockdown of miR-128 restored the altered proliferation, migration and invasion and the expression of ZEB1 and E-cadherin caused by knockdown of PVT1.

CONCLUSIONS

High levels of PVT1 in serum were correlated with postoperative metastasis and a poor prognosis. PVT1 promoted ESCC progression via the miR-128/ZEB1/E-cadherin axis.

摘要

目的

确认 PVT1 在食管癌肿瘤组织和血清中的预后标志物价值，并阐明其机制。

方法

本研究分析了 2015 年 1 月 1 日至 2016 年 12 月 31 日接受手术治疗并获得食管鳞癌病理诊断的 76 例患者的数据。通过 qRT-PCR 检测肿瘤组织和血清中的 PVT1 水平。从病历中提取患者数据，并进行随访评估。通过 CCK-8 和 Transwell 检测稳定敲低 PVT1 细胞系中 PVT1 在增殖、迁移和侵袭中的作用。通过 qRT-PCR 和 Western blot 检测 PVT1 促进食管癌的信号通路。

结果

PVT1 在食管癌组织中呈高表达，高水平的 PVT1 与淋巴转移、高 TNM 分期和术后转移相关。组织中高水平的 PVT1 与无复发生存率（MFS）较差相关（HR：2.578，95%CI：1.369-4.853）。血清中高水平的 PVT1 与术后转移相关。血清中高水平的 PVT1 与总生存（OS）较差（HR：2.124，95%CI：1.078-4.186）和 MFS 较差（HR：2.786，95%CI：1.557-4.985）相关。敲低 PVT1 降低了食管癌细胞系的细胞增殖、迁移和侵袭能力。敲低 PVT1 后 ZEB1 的表达明显下调，E-cadherin 的表达增加。敲低 miR-128 恢复了由 PVT1 敲低引起的改变的增殖、迁移和侵袭以及 ZEB1 和 E-cadherin 的表达。