TRIM11, a direct target of miR-24-3p, promotes cell proliferation and inhibits apoptosis in colon cancer.

Yan Yin,Jian-Zhe Li,Yi Sang,Min Zhou,Lijuan Liu,Si-Wei Li,Yin Chen,Jun Zhong

doi:10.18632/oncotarget.13550

Abstract

TRIM11 (tripartite motif-containing protein 11) is an E3 ubiquitin ligase recently identified as an oncogene in malignant glioma and lung cancer. In the present study, we report that expression of TRIM11 was increased in colon cancer (CC) tissue relative to paired normal tissues and that higher TRIM11 levels predicted poor overall survival (OS) and disease-free survival (DFS) in CC patients. Mechanistically, we showed that miR-24-3p downregulation contributes to TRIM11 upregulation in CC. We also demonstrated that TRIM11 overexpression promotes cell proliferation and colony formation and inhibits apoptosis in CC, while knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited cell proliferation and induced apoptosis. Silencing TRIM11 in vivo decreased tumor growth. These findings indicate that TRIM11 facilitates CC progression by promoting cell proliferation and inhibiting apoptosis and that the novel miR-24-3p/TRIM11 axis may be a useful new target for treating patients with CC.

Highlights

Colon cancer (CC) is the third most common cancer and the fourth leading cause of cancer-related deaths worldwide [1,2,3]
To investigate whether TRIM11 expression can serve as a novel prognostic marker for CC patients, based on the TRIM11 expression levels reported in a large public clinical microarray database, CC samples were subdivided into two groups and the associated overall survival (OS) and disease-free survival (DFS) were analyzed
We demonstrate for the first time that TRIM11 is a key player in CC progression; we show that downregulation of miR-24-3p is at least partly responsible for the upregulation of TRIM11 in CC cells

Summary

Introduction

Colon cancer (CC) is the third most common cancer and the fourth leading cause of cancer-related deaths worldwide [1,2,3]. The dysregulation of oncogenes or tumor suppressor genes is tightly correlated with CC initiation, progression, and resistance to therapy, of all of which involve changes in the biological characteristics of cancer cells, including cell growth, apoptosis, migration, invasion, and metabolism [4, 5]. TRIM family proteins are involved in many biological processes, and changes in their abundance or activity are associated with several pathological conditions, including viral infections, developmental and neurodegenerative disorders, and cancers [7, 8]. TRIM11 interacts with Phox2b, a homeodomain transcription factor that modulates the development of noradrenergic neurons, and increases www.impactjournals.com/oncotarget expression of dopamine β-hydroxylase gene [12]. TRIM11 is upregulated in malignant gliomas, where it promotes proliferation, invasion, migration, and tumor growth by increasing the accumulation of EGFR and activity of MAPK cascade [13]. TRIM11 is highly expressed in lung cancer tissues and cell lines, and higher expression of TRIM11 is correlated with the poorer prognosis in lung cancer patients [14]

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