Abstract
MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that are often found at chromosomal breakpoints and play a vital role in human cancer. Our previous study found that miR-550a, a frequently amplified miRNA on 7p14.3, was upregulated in hepatocellular carcinoma (HCC). However, the possible functions and molecular mechanisms of miR-550a in HCC remain unknown. In this study, gain-of-function and loss-of-function assays revealed that miR-550a markedly promoted HCC cell migration and invasion. In addition, we discovered that cytoplasmic polyadenylation element binding protein 4 (CPEB4) was a potential target of miR-550a in HCC. Further analyses showed that knockdown of CPEB4 expression significantly facilitated HCC cell migration and invasion, which phenocopied the effects of miR-550a on HCC cells. Moreover, a decrease in CPEB4 expression mediated miR-550a-induced liver cancer cell migration and invasion. Interestingly, CPEB4 is frequently downregulated in HCC, and its expression levels correlate with the overall survival of HCC patients. Together, these results suggested that this newly identified miR-550a-CPEB4 axis may be involved in HCC cell metastasis. Moreover, the expression levels of CPEB4 could be used to predict outcomes in HCC patients. Our findings provide novel potential targets for HCC therapy and prognosis.
Highlights
MicroRNAs are small, single-stranded, non-coding RNAs that are highly conserved between species [1]
The results indicated that miR550a expression was upregulated in 58% of Hepatocellular carcinoma (HCC) tissues compared with the noncancerous liver tissues (Figure 1A, B)
Cell Counting Kit-8 (CCK-8) assays suggested that miR-550a did not influence HCC cell growth (Figure S2A, B), and transwell assays with or without Matrigel indicated that miR-550a markedly induced migration and invasion in HCC cell lines (Figure S3A, B)
Summary
MicroRNAs (miRNAs) are small, single-stranded, non-coding RNAs that are highly conserved between species [1]. They are key post-transcriptional regulators of gene expression that act mainly via binding to the 39 untranslated regions (39 UTRs) of target mRNAs and participate in various biological processes [2,3,4,5]. In the last decade, emerging evidence has indicated that miRNAs are differentially expressed and play critical roles in many cancers [6,9]. Hepatocellular carcinoma (HCC) is one of the most prevalent cancers, among East Asian and Southeast Asian populations [10]. As one hallmark of cancer, genomic instability leads to the over- or under-expression of genes and enables cancer cells to acquire multiple mutations, which leads to the initiation and development of cancer phenotypes [6,12,13,14]
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