RUNX2 通过调控 COL1A1 促进胃癌的恶性进展。

RUNX2 promotes malignant progression in gastric cancer by regulating COL1A1.

机构信息

Department of Pathology, Tianjin Medical University, Tianjin, China.

Department of Gastrointestinal Surgery, Tianjin Nankai Hospital, Tianjin, China.

出版信息

Cancer Biomark. 2021;31(3):227-238. doi: 10.3233/CBM-200472.

DOI:10.3233/CBM-200472

PMID:33896817

Abstract

BACKGROUND

Runt-related transcription factor 2 (RUNX2) is an important gene that has been implicated in the progression of human cancer. Aberrant expression of RUNX2 predicts gastric cancer (GC) metastasis. However, the molecular mechanism of RUNX2 remains unknown.

OBJECTIVE

We hypothesize that RUNX2 promotes GC metastasis by regulating the extracellular matrix component collagen type I alpha 1 (COL1A1).

METHODS

The GEPIA database and immunohistochemical staining of 60 GC tissues were used to analyse the correlations between RUNX2 or COL1A1 expression and clinicopathological features, and the Kaplan-Meier method was used to evaluate survival. RT-PCR, western blotting and immunofluorescence were used to detect RUNX2 and COL1A1 expression in GC cells. Migration and invasion assays were performed to assess the influence of RUNX2 and COL1A1 on metastasis.

RESULTS

RUNX2 and COL1A1 were highly expressed at both the gene and protein levels in GC, and patients who were positive for RUNX2 and COL1A1 had shorter survival. RUNX2 and COL1A1 expression linearly correlated with each other (r= 0.15, p< 0.01) and with clinical stage and lymph node metastasis (p< 0.05). Overexpressing RUNX2in vitro enhanced COL1A1 expression and promoted GC cell invasion and migration, whereas COL1A1 knockdown inhibited the increase in cell metastatic capacity promoted by RUNX2. In vivo, GC cells overexpressing RUNX2 promoted lung metastasis, and the downregulation of COL1A1 reduced the metastasis promoted by RUNX2.

CONCLUSIONS

RUNX2 may promote GC metastasis by regulating COL1A1. RUNX2/COL1A1 can be employed as a novel target for therapy in GC.

摘要

背景

runt 相关转录因子 2（RUNX2）是一个重要的基因，与人类癌症的进展有关。RUNX2 的异常表达预示着胃癌（GC）的转移。然而，RUNX2 的分子机制尚不清楚。

目的

我们假设 RUNX2 通过调节细胞外基质成分胶原 I 型 α1（COL1A1）促进 GC 转移。

方法

使用 GEPIA 数据库和 60 例 GC 组织的免疫组织化学染色来分析 RUNX2 或 COL1A1 表达与临床病理特征的相关性，并使用 Kaplan-Meier 法评估生存情况。使用 RT-PCR、western blot 和免疫荧光检测 GC 细胞中 RUNX2 和 COL1A1 的表达。进行迁移和侵袭实验以评估 RUNX2 和 COL1A1 对转移的影响。

结果

在 GC 中，RUNX2 和 COL1A1 在基因和蛋白水平上均高度表达，RUNX2 和 COL1A1 阳性的患者生存时间更短。RUNX2 和 COL1A1 的表达呈线性相关（r=0.15，p<0.01），与临床分期和淋巴结转移相关（p<0.05）。体外过表达 RUNX2 增强了 COL1A1 的表达，促进了 GC 细胞的侵袭和迁移，而 COL1A1 的敲低抑制了 RUNX2 促进的细胞转移能力的增加。体内实验中，过表达 RUNX2 的 GC 细胞促进了肺转移，下调 COL1A1 减少了 RUNX2 促进的转移。