Coordinative control of G2/M phase of the cell cycle by non-coding RNAs in hepatocellular carcinoma

Jun Shi,Jing Xu,Keooudone Thammavong,Jiahong Dong,Guangqiang Ye,Xuedong Wang,Guoliang Zhao,Chunhui Ye

doi:10.7717/peerj.5787

Abstract

ObjectiveTo investigate the interaction of non-coding RNAs (ncRNAs) in hepatocellular carcinoma.MethodsWe compared the ncRNAs and mRNAs expression profiles of hepatocellular carcinoma and adjacent tissue by microarray and RT-PCR. The relationship between different ncRNAs and mRNA was analyzed using bioinformatics tools. A regulatory model of ncRNAs in hepatocellular carcinoma cells was developed.ResultsA total of 1,704 differentially expressed lncRNAs, 57 miRNAs, and 2,093 mRNAs were identified by microarray analyses. There is a co-expression relationship between two ncRNAs (miRNA-125b-2-3p and lncRNA P26302). Bioinformatics analysis demonstrated cyclin-dependent kinases 1 and CyclinA2 as potential targets of miR-125b-2-3p and Polo-like kinase 1 as potential target of lncRNAP26302. All three gene are important components in the G2/M phase of cell cycle. Subsequently real-time polymerase chain reaction (PCR) studies confirmed these microarray results.ConclusionMiR-125b-2-3p and lncRNAP26302 may affect the G2/M phase of the cell cycle through the regulation of their respective target genes. This study shows a role of ncRNAs in pathogenesis of hepatocellular carcinoma at molecular level, providing a basis for the future investigation aiming at early diagnosis and novel treatment of hepatocellular carcinoma.

Highlights

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for 85–90% of all primary livery cancer cases
The same samples were used for gene expression profiling using the JingxinÒ human long ncRNA (lncRNA) + mRNA V4.0 chip
The results showed that the expression of miR125b-2-3p was significantly lower in HCC tissues than in adjacent tissues (PmiR125b-2-3p = 0.0052), while the expression levels of lncRNAp26302, cyclin-dependent kinases 1 (CDK1), cyclin A2, and Polo-like kinase 1 (PLK1) were significantly higher in HCC tissues than in adjacent tissues (PP26302 = 0.0255; PCCNA 2 = 0.028; PCDK 1 = 0.0171; Pplk 1 = 0.0267)

Summary

Introduction

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, accounting for 85–90% of all primary livery cancer cases. Among the world’s most common malignancies, the incidence of HCC is ranked sixth, and its mortality rate is ranked third (Torre et al, 2015). The high mortality rate is mainly due to the strong invasive and metastatic capacity of HCC cells. How to cite this article Shi et al (2018), Coordinative control of G2/M phase of the cell cycle by non-coding RNAs in hepatocellular carcinoma. Diagnosis is the key to effective treatment of liver cancer. It is important to find effective early diagnosis markers of liver cancer. A large number of studies have suggested that non-coding RNAs (ncRNA) are related to the occurrence of tumors, providing a new research direction for the diagnosis and treatment of liver cancer (Mattick & Makunin, 2006)

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