Original articlemiR-184 functions as an oncogenic regulator in hepatocellular carcinoma (HCC)
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)
- et al.
Primary liver cancer: worldwide incidence and trends
Gastroenterology
(2004) - et al.
Identification of tissue-specific microRNAs from mouse
Curr Biol
(2002) - et al.
Diagnostic and prognostic potential of differentially expressed miRNAs between metastatic and non-metastatic renal cell carcinoma at the time of nephrectomy
Clin Chim Acta
(2013) - et al.
Expression profiling the microRNA response to epileptic preconditioning identifies miR-184 as a modulator of seizure-induced neuronal death
Exp Neurol
(2012) - et al.
Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters
BMC cancer
(2009) Gene regulation by transcription factors and microRNAs
Science
(2008)- et al.
MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma
Hepatology
(2009) - et al.
Downregulation of miR-122 in the rodent and human hepatocellular carcinomas
J Cell Biochem
(2006)
Cited by (53)
Harnessing function of EMT in hepatocellular carcinoma: From biological view to nanotechnological standpoint
2023, Environmental ResearchmicroRNA, epi-microRNA, and cancer
2023, Epigenetic Cancer Therapy, Second EditionmiR-383 inhibits cell growth and promotes cell apoptosis in hepatocellular carcinoma by targeting IL-17 via STAT3 signaling pathway
2019, Biomedicine and PharmacotherapyCitation Excerpt :In the case of HCC, Klingenberg et al summaried 16 miRNA expressions were dysregulated, mainly up-regulated [10]. Integrating with many studies concerning the functional role of miRNA in HCC, oncogenetic miRNAs were revealed, including miR-184 [11], miR-10b-3p [12]. Meanwhile, suppressive miRNAs were following, miR-122 [13], miR-146a-5p [14], miR-143 [15], miR-1 [16], miR-144 [17], miR-940 [18].
Biomarker identification in clear cell renal cell carcinoma based on miRNA-seq and digital gene expression-seq data
2018, GeneCitation Excerpt :Moreover, miRNA-184 was found to interact with miRNA-429 and miRNA-206 through CCND1 in the miRNA regulatory network. miRNA-184 has been reported to be associated with hepatocellular carcinoma and neuroblastoma (Tivnan et al., 2010; Gao et al., 2014). Interestingly, miRNA-184 was not detected in 786-O cells after experimental verification because of its too low expression level.
Circ_0004913 Inhibits Cell Growth, Metastasis, and Glycolysis by Absorbing miR-184 to Regulate HAMP in Hepatocellular Carcinoma
2023, Cancer Biotherapy and RadiopharmaceuticalsmicroRNA-184 in the landscape of human malignancies: a review to roles and clinical significance
2023, Cell Death Discovery