Dexmedetomidine promotes apoptosis and suppresses proliferation of hepatocellular carcinoma cells via microRNA-130a/EGR1 axis

Lei Zhou,Wen Ouyang,Jia Chen,Huiyin Deng,Tunliang Li,Kuan Hu,Juanni Li,Xing Liu,Yongzhong Tang,Xinlin Yin

doi:10.1038/s41420-021-00805-5

Abstract

Accumulating evidence has revealed the role of microRNAs (miRs) in hepatocellular carcinoma (HCC). Dexmedetomidine, a highly selective α2-adrenergic agonist, is widely used in perioperative settings for analgesia and sedation. Herein, we aimed to determine whether dexmedetomidine might directly regulate miR-130a/early growth response 1 (EGR1) axis in HCC and explore the related mechanisms. miR-130a and EGR1 expression were determined in HCC tissues and their correlation was evaluated. Human HCC cell line HCCLM3 was selected. Upon the determination of the optimal concentration of dexmedetomidine, HCCLM3 cells were treated with dexmedetomidine, miR-130a- or EGR1-related oligonucleotides or plasmids were transfected into cells to explore their functions in cell biological behaviors. miR-130a and EGR1 levels in cells were tested. The targeting relationship between miR-130a and EGR1 was verified. miR-130a was inhibited while EGR1 was elevated in HCC tissues and they were negatively correlated. EGR1 was targeted by miR-130a. With the increase of dexmedetomidine concentration, HCCLM3 cell viability was correspondingly inhibited, miR-130a expression was elevated and EGR1 expression was decreased. Dexmedetomidine, upregulating miR-130a or downregulating EGR1 inhibited proliferation, invasion and migration, and promoted apoptosis of HCCLM3 cells. MiR-130a upregulation/downregulation enhanced/impaired the effect of dexmedetomidine on cell biological behaviors. Our study provides evidence that raising miR-130a enhances the inhibitory effects of dexmedetomidine on HCC cellular growth via inhibiting EGR1. Thus, miR-130a may be a potential candidate for the treatment of HCC.

Highlights

Hepatocellular carcinoma (HCC) is the commonest primary malignant tumor of hepatocytes, the fifth frequent cancer and the third leading cause of cancer-related mortality globally, after lung cancer and stomach cancer [1]
MiR-130a is downregulated and early growth response 1 (EGR1) is upregulated in hepatocellular carcinoma (HCC); EGR1 expression in HCC tissues and adjacent normal tissues was miR-130a targets EGR1 tested by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry
It was manifested that EGR1 was expression group and miR-130a low expression group using the upregulated in HCC cell lines

Summary

Introduction

Hepatocellular carcinoma (HCC) is the commonest primary malignant tumor of hepatocytes, the fifth frequent cancer and the third leading cause of cancer-related mortality globally, after lung cancer and stomach cancer [1]. HCC most commonly occurs with chronic alcohol abuse, hepatitis C virus (HCV), or nonalcoholic fatty liver disease [3]. Locoregional therapy, hepatic resection, and liver transplantation may be effective in the early stages of the tumor which account for less than 30% of patients, while transarterial chemoembolization is the first-line treatment for advanced HCC [4]. Metastasis is the major cause of the high mortality of HCC patients post-surgical resection [5].

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