Abstract

Inhibition of aerobic glycolysis is a hopeful method for cancer treatment. In this study, we aimed to explore LINC00665/miR-214-3p/MAPK1 role in regulating cell viability and aerobic glycolysis in hepatocellular carcinoma (HCC). The expressions of LINC00665 in 50 paired HCC tissues and normal tissues were determined by qRT-PCR. Pearson analysis was applied to evaluate the association between the expression levels of miR-214-3p, LINC00665, and MAPK1 in HCC tissues. The interactions between miR-214-3p and LINC00665 or MAPK1 were determined by luciferase reporter assay and RNA immunoprecipitation. CCK-8 and colony formation assays were used for cell viability evaluation. Lactate production, glucose consumption, and ATP levels were measured to assess Warburg effect. The results showed that LINC00665 was overexpressed in HCC, which positively associated with MAPK1 level and negatively associated with miR-214-3p level in HCC tissues. Overexpression of LINC00665 led to significant enhancements in cell viability and colony formation, whereas this effect was weakened when miR-214-3p was overexpressed or MAPK1 was downregulated. In addition, deletion of LINC00665 expression repressed tumor formation in vivo. Mechanically, LINC00665 increased MAPK1 expression through binding to miR-214-3p. Collectively, this study revealed that LINC00665 accelerated cell growth and Warburg effect through sponging miR-214-3p to increase MAPK1 expression in HCC.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most common malignancies [1]

  • We found that miR-214-3p had putative binding sites with LINC00665, indicating that the LINC00665/miR-214-3p/ mitogen-activated protein kinase 1 (MAPK1) axis might take part in HCC progression. us, the current study was performed to reveal whether LINC00665 regulates aerobic glycolysis and cancer growth via sponging of miR-214-3p to increase MAPK1 expression in HCC

  • The results from Quantitative Reverse Transcription-PCR (qRT-PCR) and Kaplan-Meier curves showed that LINC00665 level was significantly increased in HCC tissues, which was predicted with a shorter overall survival (Figures 1(c) and 1(d))

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignancies [1]. Most patients with HCC show a dismal prognosis due to the high rates of metastasis and recurrence [2]. Due to the difficulties in early diagnosis and the absence of effective treatment methods, the 5-year survival rate of HCC remains less than 20% [3]. Known as “Warburg effect,” is a trait of cancer cells. Cancer cells obtain energy to maintain the rapid growth through increasing of the uptake and consumption of glucose and enhancing glycolytic activity and excessive lactate secretion even in the presence of high oxygen concentration [4]. Evidence has demonstrated that Warburg effect plays crucial roles in accelerating cancer cell growth, migration, and drug resistance [5,6]. Inhibition of aerobic glycolysis is of hope for oncotherapy including HCC [7,8 ]

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