MicroRNA miR-147b promotes tumor growth via targeting UBE2N in hepatocellular carcinoma.

En Zhang,Qin Liu,Yong Wang,Ning Li,Xiuli Jin,Li He,Hui Wang

doi:10.18632/oncotarget.23120

Abstract

As the subfamily of noncoding RNA, microRNAs (miRNAs) broadly regulate the development of cancers, while their dysregulation and function in human hepatocellular carcinoma (HCC) remains largely unclear. Here, we found the expression level of microRNA-147b (miR-147b) is increased aberrantly in HCC tumor tissues, and its expression positively correlates to the tumor severity. In both MTT and colony formation assay, knockdown of miR-147b dramatically inhibits in vitro proliferation of HCC cell lines. More interestingly, we also performed in vivo tumorigenesis assay and found that miR-147b can regulate in vivo tumorigenesis in nude mice xenograft models. The ubiquitin-conjugating enzyme E2N (UBE2N) was identified directly and functionally targeted by miR-147b. The mRNA level of UBE2N is increased in HCC tumors or cell lines. Restoring UBE2N expression level in tumor cells leads to inhibition of cell proliferation, which mimics the effect upon miR-147b knockdown in the same cells. These data elucidated the oncogenic role of miR-147b in HCC development and progression with therapeutic target potentials.

Highlights

Hepatocellular carcinoma (HCC) is one kind of primary liver cancers with high mortality, it is the most common type of cancer worldwide, especially in Asia, African and south Europe [1]
Quantitative PCR analysis reveals that miR-147b showed a 2-fold upregulation in the hepatocellular carcinoma (HCC) group compared to nontumor controls or HCC adjacent tissues (Figure 1C)
To further explore if miR-147b is involved in HCC pathogenesis, the expression level of miR-147b was analyzed in HCC tumor samples with different AJCC disease stages [8, 9]

Summary

Introduction

Hepatocellular carcinoma (HCC) is one kind of primary liver cancers with high mortality, it is the most common type of cancer worldwide, especially in Asia, African and south Europe [1]. MicroRNAs belong to the family of noncoding RNAs, it is encoded by cell genome with 22 nucleotides in length, miRNA can posttranscriptional regulate gene expression both in plants and animals. Since the seed sequence of one miRNA can base paired with multiple different mRNA molecules, this characteristics enable the miRNA family members can regulate even up to one third of the protein coding transcripts in the whole human genome. It attracted broad attention and interests of the researchers to uncover their functions in biological process and all kinds of disease conditions. In HCC, previous reports found the upregulation or downregulation of miRNA, which indicated that their functions were as important as the protein coding genes [6]

Methods

Results

Conclusion