MiR-128 Functions as an OncomiR for the Downregulation of HIC1 in Breast Cancer.

Yan Li,Xinghua Han,Xiabo Shen,Ying Wang

doi:10.3389/fphar.2019.01202

Abstract

Hypermethylated in cancer 1 (HIC1) is continually decreased in breast cancer. However, the underlying molecular basis of the upstream regulation of HIC1 remains elusive. Here, we showed that HIC1 was downregulated in breast cancer tissues. Bioinformatics analysis identified that miR-128 might potentially target HIC1. HIC1 was proved as the target gene of miR-128 by overexpressing or knocking down miR-128. Additionally, we observed that HIC1 suppression by miR-128 increased cell invasion, proliferation, and reduced apoptosis. Lastly, we found that miR-128 accelerated tumor growth in xenograft mice by inhibiting HIC1. Altogether, this study presents the first evidence that miR-128 suppresses the expression of HIC1 to accelerate breast cancerogenesis.

Highlights

Breast cancer is one of the most common type of cancer worldwide and the chief cause of death in women (Torre et al, 2015)
hypermethylated in cancer 1 (HIC1) is continually silenced in human cancers, including breast cancer, prostate cancer, colorectal cancer, liver cancer, and lung cancer (Morton et al, 1996; Chen et al, 2005; Jin et al, 2017; Wang et al, 2017), and this is assumed to be ascribed to promoter hypermethylation (Zhang et al, 2010)
We analyzed the patient samples in TCGA database, the results discovered that HIC1 was significantly down-expressed in breast cancers (Figures 1A, B), suggesting that the malignancy of breast cancer was related to HIC1 abnormal expression

Summary

Introduction

Breast cancer is one of the most common type of cancer worldwide and the chief cause of death in women (Torre et al, 2015). The hypermethylation of HIC1 promoter is detected in tumors and in normal breast ductal (Zhang et al, 2010), prostate epithelium tissues (Morton et al, 1996), and brain (Rood et al, 2002). These findings indicate that a previously uncharacterized regulatory mechanism rather than hypermethylation is involved in HIC1 repression

Methods

Results

Conclusion