circHIPK3 regulates cell proliferation and migration by sponging microRNA-124 and regulating serine/threonine kinase 3 expression in esophageal squamous cell carcinoma

Abstract

Circular RNAs (circRNAs) are a type of important non-coding RNAs that widely involve in the physiological and pathophysiological process. Recent research has established a link between circHIPK3 and the malignant activity of cancer cells. However, circHIPK3’ role in esophageal squamous cell carcinoma (ESCC) still needs more focus. To determine the prognostic value of circHIPK3 in patients with ESCC, the expression of circHIPK3 was quantified in 32 pairs of ESCC using real-time polymerase chain reaction (RT-qPCR). Then, the correlation between circHIPK3 expression and clinical characteristics of patients was also analyzed. The function of circHIPK3 in the development of ESCC was investigated using cell biology studies and bioinformatics. The results showed that the expression of circHIPK3 was considerably higher in tumor tissues from ESCC patients than that of adjacent tissues, which was associated with a poor prognosis. Additionally, silencing of circHIPK3 expression retarded esophageal cancer cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro , as well as the growth in vivo . Mechanistically, we discovered that circHIPK3 behaved like a sponge, absorbing microRNA-124 (miR-124) and promoting serine/threonine kinase 3 ( AKT3 ) expression. Our findings indicate that circHIPK3 acts as an oncogene in ESCC and that the circHIPK3- AKT3 axis may be a therapeutic target for patients with ESCC.

Understanding the Dual Roles of CircHIPK3 in Tumorigenesis and Tumor Progression

“…Mechanistically, circHIPK3 was identified to promote ESCC development through the miR-599/c-MYC axis 71 . Besides, Yao et al found that circHIPK3 facilitated AKT serine/threonine kinase 3 (AKT3) expression by sponging miR-124, thus forming the circHIPK3/miR-124/AKT3 axis to promote ESCC cell proliferation, migration, and epithelial-mesenchymal transition 72 .…”

The necroptosis related gene LGALS3 can be used as a biomarker for the adverse progression from chronic HBV infection to HCC

“…In this study, we systematically analyzed the expression level and correlation of NRGs in HBV-HCC and paracarcinoma tissues. Gene ontology analysis revealed 24 DENRGs that were enriched for pathways related to the proliferation and migration of tumor cells ( 17 , 18 ). In addition to HBV-HCC tissues, LGALS3 expression was also upregulated in CHI tissues and tissues with high fibrosis scores.…”

The Diagnostic and Therapeutic Role of Circular RNA HIPK3 in Human Diseases

“…Yao et al reported that an elevated level of circHIKP3 in ESCC cells remarkably absorbed miR-599 expression and significantly stimulated c-MYC expression, leading to cell growth and metastasis [ 33 ]. Yao and colleagues validated that miR-124 functioned as the sponged miRNA in this case and serine/threonine kinase 3 (AKT3) was enhanced under the modulation of circHIPK3, which further triggered ESCC cell growth and metastasis [ 34 ].…”