Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most frequent cause of cancer‐related death. The IRX5 transcription factor plays a different role in multiple cancers and contributes to the development of many tumours. However, little is known about the molecular mechanisms of IRX5 in HCC. In this study, we found that IRX5 was abnormally upregulated in HCC tissues compared with adjacent normal tissues. IRX5 promoted HCC cell proliferation and upregulated the expression of cyclin D1 and knockdown of IRX5 suppressed tumorigenicity in vivo. Furthermore, knockdown of IRX5 increased p53 and Bax expression and decreased Bcl‐2 expression. Thus, IRX5 suppressed apoptosis in HCC cells by inhibiting the p53 signalling pathway, indicating its role as a treatment target for HCC.Significance of the studyOur study demonstrated that IRX5 was abnormally upregulated in HCC tissues compared with adjacent normal tissues. IRX5 promoted HCC cell proliferation and upregulated the expression of cyclin D1, and knockdown of IRX5 suppressed tumorigenicity in vivo. Furthermore, knockdown of IRX5 increased p53 and Bax expression and decreased Bcl‐2 expression. IRX5 suppressed apoptosis in HCC cells by inhibiting the p53 signalling pathway, indicating its role as a treatment target for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most frequent cause of cancer-related death
We found that IRX5 was abnormally upregulated in HCC tissues compared with adjacent normal tissues
Significance of the study: Our study demonstrated that IRX5 was abnormally upregulated in HCC tissues compared with adjacent normal tissues
Summary
Liver cancer was the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide in 2018,1 with approximately 841 000 new cases and 782 000 deaths annually.[2]. Iroquois homeobox (Irx) genes play pivotal roles in normal embryonic cell patterning and the development of malignancies.[8] The Irx family is composed of six genes in humans and mice, including two clusters, IrxA (Irx[1], Irx[2] and Irx4) located on chromosome 5 and IrxB (Irx[3], Irx[5] and Irx6) located on chromosome 16.9 IRX5 encodes a transcription factor and is a highly conserved member of the Iroquois homeobox gene family.[8] IRX5 plays a different role in multiple cancers, contributing to the development of many tumours by acting as an important transcription factor regulating key regulatory genes that control cell growth, invasion, migration and apoptosis. Recent data suggest that IRX5 is a transcription factor that remarkably promotes tongue squamous cell carcinoma tumour growth by targeting the osteopontin (OPN) promoter and activating the NF-κB pathway.[8] Our previous study showed that CRNDE acted as a tumour oncogene by promoting the oncogenic properties of human HCC and revealed a novel CRNDE-miR-136-5p-IRX5 regulatory network in HCC.[3]. We will discuss the properties of IRX5 in the p53 signalling pathway
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