MicroRNA-505 suppresses proliferation and invasion in hepatoma cells by directly targeting high-mobility group box 1
Introduction
Hepatocellular carcinoma (HCC) is a malignant disease in liver, including primary HCC and metastatic HCC. Viral infection induced by hepatitis B virus (HBV) and/or hepatitis C virus (HBV) are the major complications of primary HCC development [1]. Metastatic HCC is often found in patients with advanced metastatic cancer [2]. HCC is the sixth most common malignancy and the third fatal cancer worldwide. One of the hallmarks of cancer is sustained cell growth and proliferation, which is leading to tumor growth and responsible for cancer-related deaths. Metastasis is another hallmark of cancer. HCC is one of the most aggressive tumors with high rate of tumor cell metastasis and postsurgical recurrence [3], [4]. Although great efforts have been made in HCC therapeutic, the treatment methods are still limited due to poor prognosis. Therefore, identifying effective treatment strategies and understanding the molecular mechanisms responsible for the pathogenesis of HCC are still urgent needs.
MicroRNAs (miRNAs) are small (~ 21-nucleotide) endogenous RNAs that can negatively regulate gene expression in animals and plants by base pairing to mRNAs for cleavage or translational repression [5]. Up to now, microRNAs have been shown to participate in the regulation of almost every cellular process in mammals, and have become a research focus in molecular biology [6], [7]. MiRNA alterations are involved in the initiation and progression of human cancers [8], and many miRNAs have been identified as oncogenes or tumor suppressors [9], [10], [11], [12]. The association of miRNAs with cancer is apparently becoming an important aspect of their biological significance and highlights their potential importance for clinical applications in cancers [13], [14].
Altered miRNA expression was detected in the tumor tissues or serum of the HCC patients. For example, Lin et al. analyzed the microRNA expression in liver cancer tissues and normal control using the microarray analysis. They found 221 miRNAs expression were altered in the liver cancer tissues when compared with normal control. And five of them (including hsa-miR-15b, hsa-miR-1975, hsa-miR-199a-3p, hsa-miR-199b-3p and hsa-miR-421) may be involved in the pathogenesis of HCC [15].
A recent research showed that seven miRNAs (including miR-29a, miR-29c, miR-133a, miR-143, miR-145, miR-192, and miR-505) were differentially expressed in the serum of early HCC patient [16]. There differentially expressed miRNAs may involve in the pathogenesis of HCC and might be potential molecular markers for HCC screening. Yamamoto et al. show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis in human breast cancer cells [17]. However, the expression of miR-505 in HCC tissues or hepatoma cell lines, as well as the effect of miR-505 in the pathogenesis of HCC remains unclear.
In the present study, we intended to determine the expression of miR-505 in several hepatoma cells, and further to elucidate the probably effect and underlying mechanism of miR-505 in HCC in vitro.
Section snippets
Specimens
Fresh hepatoma tissue specimens and paired adjacent tissue samples were collected from 10 patients who were performed hepatoma resection operation in our hospital between March 2015 and November 2015. The specimens were preserved in liquid nitrogen immediately for subsequent testing. The specimens collection procedure with informed patient consent and approval of the Medical Ethics Committee.
Cell culture
Normal liver epithelial cell LO2 and HCC cell lines, QGY-7703, SMMC-7721 and MHCC97 were purchased from
MiR-505 is downregulated in different hepatoma cell lines
The expression of miR-505 in hepatoma tissues and three hepatocyte cell lines were detected using the real-time PCR analysis. As shown in Fig. 1A, the expressions of miR-505 in normal human hepatoma tissues were lower than that in the normal adjacent tissues. Moreover, the levels of miR-505 in three hepatoma cell lines were significantly lower than that in normal cells (Fig. 1B). It is noteworthy that the expression of miR-505 in MHCC97 cell was higher than those in QGY-7703 and SMMC-7721 cells
Discussion
As the improvement in HCC treatment strategies, patients with HCC have improved through the use of a variety of HCC treatment methods, such as surgical hepatic resection, liver transplantation, anti-viral agents, percutaneous ethanol injection, radiofrequency ablation, trans-catheter arterial chemoembolization, and molecular-target drugs [20], [21]. However, due to the invasion of HCC metastasis, the efficacy of these therapeutic interventions significantly reduced and a 5-year overall survival
Conclusions
In summary, the current study investigated that miR-505 was downregulated in several HCC cell lines and could inhibit proliferation and invasion of MHCC97 cell lines via targeting HMGB1. The results of the present study suggested the potential tumor suppressor roles of miR-505 in HCC.
Formatting of funding sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgements
None.
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