Original article
miR-184 functions as an oncogenic regulator in hepatocellular carcinoma (HCC)

https://doi.org/10.1016/j.biopha.2013.09.005Get rights and content

Abstract

Dysregulation of miRNAs has been proved to play a key role in carcinogenesis or tumor progression. In hepatocellular carcinoma (HCC), a number of miRNAs was reported to be related to the occurrence and development of HCC. Especially, miRNA-122, a liver-specific miRNA, has been elaborated its role in HCC. However, these studies was not involved in the effect of miRNA-184 on HCC. In the present study, we aimed to detect the miRNA-184 expression in HCC tissues and further evaluate the in vitro effect of miR-184 inhibition in HCC cells HepG2. We found that miR-184 expression was significantly high in HCC tissues, but INPPL1 expression was obviously low. Subsequently, INPPL1 was identified as a target of miRNA-184 by bioinformatics and dual luciferase assay. Moreover, after transfected with anti-miR-184 in HepG2 cells, INPPL1 expression was significantly decreased both at mRNA and protein levels. Additionally, we also proved that miR-184 silencing inhibited cellular proliferation by over expressing INPPL1 and induced HepG2 apoptosis by caspase 3/7. Together, our result was shown that miR-184 might play a part in proliferation of HCC cells by INPPL1 loss and act as antiapoptotic factor in the development of HCC by inhibiting the activities of caspases 3/7. Therefore, further elucidation of miRNA-184 silencing is helpful for understanding the pathogenesis of HCC and devising new strategies for its prevention and therapy.

Introduction

Hepatocellular carcinoma (HCC), which affects hundreds of millions of people worldwide, is one of the ten top malignant tumors in the world, with high morbidity and mortality [1]. Especially in China, the mortality rate of HCC is the second highest. The 5-year survival rate of HCC is below 5% and each year almost 600,000 HCC patients die [2]. Otherwise, the common tool for HCC early diagnosis is B-mode ultrasound, CT, the detection of alpha-fetoprotein (AFP), but it is easy to be misdiagnosed. Therefore, the investigation into the pathogenesis and diagnosis of HCC is of great significance.

The discovery of miRNAs provides new possibility and potential to solve the problem. MiRNAs, a class of small non-coding RNAs, induce mRNA degradation or translational repression at post-transcription by binding to the complementary sequences of their target mRNAs [3]. MiRNAs are reported to be involved in complicated life processes, thereby, impacting cell differentiation, proliferation, metabolism, stress and other processes. It has been found that miRNAs plays a key role in the development as well as the occurrence of HCC [4]. For example, miR-122, a liver-specific miRNA, is expressed at high levels in human liver and liver cell lines [5]. On the contrary, miR-122 is downregulated in HCC and HCC-derived cell lines [6], indicating that it plays a role in hepatocarcinogenesis. In addition to this, some miRNAs were reported to related to HCC, such as miRNA-34a [7], miRNA-320 [8], miRNA-221 [9], miRNA-125b [10], miRNA-224 [11], miRNA-423 [12], and so on.

However, these studies did not involve in the effect of miRNA-184 on HCC.

In present study, we try to elaborate the role and potential mechanism of miR-184 in HCC by researching its expression and biological function in HepG2 lines.

Section snippets

Tissue samples and cell lines

Twenty-one liver tissue samples were obtained in this study, including one normal liver tissue as the control and twenty tumors diagnosed with HCC. The patients were informed consent from Affiliated Hospital of Jining Medical University, Shandong Provincial, China. The study was approved by the Ethical Committee of Hospital. Normal liver tissue was obtained from patient undergoing partial liver resection for HCC. All the samples were immediately snap frozen in liquid nitrogen after surgery and

miR-184 expression is upregulated in HCC tissues

To evaluate the expression of miRNA-184 in clinical specimens, qRT–PCR was used to detect between 20 pairs of HCC tissues and normal tissue. As shown in Fig. 1, miR-184 expression was significantly upregulated in HCC tissues compared to the normal tissue in all the detected specimens. Among them, miR-184 expression in 12 HCC tissues (60%) was greater than two-fold. It implied that miRNA-184 might be involved in the progression of HCC.

INPPL1 was identified as a target of miRNA-184

Firstly, we predicated the targets of miRNA-184 by querying

Discussion

Dysregulation of miRNAs is detected in various cancers, showing that the dysregulated miRNAs may play a key role in carcinogenesis or tumor progression. Recent studies have shown that miR-184 expression was altered in several cancers, including in squamous cell carcinoma [14], prostate cancer [15], renal cell carcinoma [16], and seizure-induced neuronal death [17]. In this study, we found that miR-184 was upregulated in HCC specimens, inferring that miRNA-184 is involved in the development of

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

References (17)

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