TRIB3 促进肝癌生长并预测不良预后。

TRIB3 promotes hepatocellular carcinoma growth and predicts poor prognosis.

机构信息

Department of Geriatrics, Department of Geriatric Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

出版信息

Cancer Biomark. 2020;29(3):307-315. doi: 10.3233/CBM-201577.

DOI:10.3233/CBM-201577

PMID:32716348

Abstract

BACKGROUND

Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which is involved a lot of cellular processes and multiple cancers, such as breast cancer, colorectal cancer, renal cell carcinomas, and lung cancer. However, the expression pattern and biological function of TRIB3 in hepatocellular carcinoma (HCC) has not yet been completely elucidated.

METHODS

The expression of TRIB3 and clinicopathological characteristics were evaluated by HCC tissue microarray and qPCR analysis. Lentivirus packaging and transfection were employed to establish cell lines with TRIB3 overexpression or knockdown. The biological functions of TRIB3 in the growth of HCC were determined using MTT and crystal violet assays. Tumor growth was monitored in a xenograft model in vivo.

RESULTS

The expression of TRIB3 was upregulated in HCC tissue samples compared to paired normal tissues in 45 patients examined by qPCR assay. TRIB3 expression was significantly correlated with HCC tumor size and prognosis in postoperative patients by analysis of the TRIB3 expression data and HCC clinical features. Forced expression of TRIB3 significantly promoted HCC growth in vitro. In contrast, downregulation of TRIB3 inhibited cell growth in vitro. Moreover, knockdown of TRIB3 suppressed tumorigenesis of HCC cells in vivo.

CONCLUSION

TRIB3 promotes growth abilities of HCC cells both in vitro and in vivo and predicts poor prognosis of HCC patients, which serves as a prognostic marker and might provide a potential therapeutic candidate for patients with HCC.

摘要

背景

Tribbles 假激酶 3（TRIB3）是 Tribbles 相关家族的成员，该家族参与了许多细胞过程和多种癌症，如乳腺癌、结直肠癌、肾细胞癌和肺癌。然而，TRIB3 在肝细胞癌（HCC）中的表达模式和生物学功能尚未完全阐明。

方法

通过 HCC 组织微阵列和 qPCR 分析评估 TRIB3 的表达和临床病理特征。使用慢病毒包装和转染建立 TRIB3 过表达或敲低的细胞系。使用 MTT 和结晶紫测定法确定 TRIB3 在 HCC 生长中的生物学功能。在体内异种移植模型中监测肿瘤生长。

结果

qPCR 检测 45 例患者的 HCC 组织样本与配对的正常组织相比，TRIB3 的表达上调。通过分析 TRIB3 表达数据和 HCC 临床特征，TRIB3 的表达与术后患者的 HCC 肿瘤大小和预后显著相关。TRIB3 的强制表达显著促进了 HCC 在体外的生长。相比之下，TRIB3 的下调抑制了体外细胞的生长。此外，TRIB3 的敲低抑制了 HCC 细胞在体内的致瘤性。