长链非编码 RNA POU3F3 通过下调长链非编码 RNA GAS5 促进肾细胞癌中癌细胞的增殖、迁移和侵袭。

LncRNA POU3F3 Promotes Cancer Cell Proliferation, Migration, and Invasion in Renal Cell Carcinoma by Downregulating LncRNA GAS5.

机构信息

Department of Urology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan City, China.

Department of Urology, Zibo Central Hospital, Zibo City, China.

出版信息

Kidney Blood Press Res. 2021;46(5):613-619. doi: 10.1159/000511174. Epub 2021 Aug 5.

DOI:10.1159/000511174

PMID:34352801

Abstract

BACKGROUND

LncRNAs play regulatory roles in diverse nephrological disorders, including renal cancer. Overexpression of lncRNA POU3F3 (POU3F3) has only been reported in esophageal squamous-cell carcinomas, indicating POU3F3 may be an oncogene in this disease. LncRNA GAS5 (GAS5) was reported to be a suppressor in various tumors. However, the roles and underlying mechanism of POU3F3 and GAS5 involved in renal cell carcinoma (RCC) remain unknown.

METHODS

Real-time quantitative PCR and in situ hybridization were performed to determine the expression of POU3F3 and GAS5 in paired tumor and adjacent healthy tissues donated by 68 RCC patients. The prognostic values of POU3F3 and GAS5 for RCC were analyzed by performing a 5-year follow-up study. Overexpression of POU3F3 and GAS5 was achieved in RCC cells to explore the interactions between them. Transwell assay and cell proliferation assay were performed to evaluate the role of POU3F3 and GAS5 in regulating RCC cell proliferation, migration, and invasion.

RESULTS

In the present study, we found that POU3F3 was upregulated while GAS5 was downregulated in tumor tissues than that in adjacent healthy tissues of patients with RCC. In situ hybridization analysis showed that POU3F3 was mostly expressed in tumor tissues, while GAS5 was mostly expressed in adjacent healthy tissues. High level of POU3F3 and low level of GAS5 were closely correlated with poor prognosis of RCC patients. Expression levels of POU3F3 and GAS5 were significantly and inversely correlated in tumor tissues but not in adjacent healthy tissues of RCC patients. Overexpression of POU3F3 mediated the downregulation of GAS5 in RCC cells, while GAS5 overexpression failed to significantly affect POU3F3 expression. Overexpression of POU3F3 led to promoted, while GAS5 overexpression led to inhibited proliferation, migration, and invasion of RCC cells. In addition, GAS5 overexpression attenuated the enhancing effects of POU3F3 overexpression on cancer cell proliferation, migration, and invasion.

CONCLUSION

POU3F3 promoted cell proliferation, migration, and invasion in RCC possibly by downregulating GAS5.

摘要

背景

长链非编码 RNA（lncRNA）在多种肾脏疾病中发挥着调节作用，包括肾癌。lncRNA POU3F3（POU3F3）的过表达仅在食管鳞状细胞癌中报道过，表明 POU3F3 可能是该疾病的癌基因。lncRNA GAS5（GAS5）被报道在各种肿瘤中是一种抑制物。然而，POU3F3 和 GAS5 在肾细胞癌（RCC）中的作用和潜在机制尚不清楚。

方法

通过实时定量 PCR 和原位杂交，检测 68 例 RCC 患者配对肿瘤和相邻正常组织中 POU3F3 和 GAS5 的表达。通过 5 年随访研究，分析 POU3F3 和 GAS5 对 RCC 的预后价值。在 RCC 细胞中过表达 POU3F3 和 GAS5，以探讨它们之间的相互作用。通过 Transwell 检测和细胞增殖检测，评估 POU3F3 和 GAS5 在调节 RCC 细胞增殖、迁移和侵袭中的作用。

结果

在本研究中，我们发现 POU3F3 在 RCC 患者肿瘤组织中的表达上调，而 GAS5 则下调。原位杂交分析显示，POU3F3 主要在肿瘤组织中表达，而 GAS5 主要在相邻的正常组织中表达。高水平的 POU3F3 和低水平的 GAS5 与 RCC 患者的不良预后密切相关。在 RCC 患者的肿瘤组织中，POU3F3 和 GAS5 的表达水平呈显著负相关，但在相邻的正常组织中无明显相关性。在 RCC 细胞中过表达 POU3F3 介导了 GAS5 的下调，而 GAS5 的过表达未能显著影响 POU3F3 的表达。过表达 POU3F3 促进了 RCC 细胞的增殖、迁移和侵袭，而过表达 GAS5 则抑制了 RCC 细胞的增殖、迁移和侵袭。此外，GAS5 的过表达减弱了 POU3F3 过表达对癌细胞增殖、迁移和侵袭的增强作用。