Heliyon (Nov 2023)
FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma
Abstract
FBXL19 is a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases and is linked to a variety of vital biological processes, such as cell proliferation, migration, and differentiation. Previous studies have identified it as an oncogene in breast cancer and glioma. However, its role in hepatocellular carcinoma (HCC) remains unclear. To comprehensively elucidate its role in tumour biology and its underlying mechanisms, a variety of sophisticated methods, including bioinformatics analysis, RNA-sequencing technique, and in vitro cell biology experiments, were used. Here, we found that FBXL19 was upregulated in patients with HCC and correlated with poor prognosis. In in vitro experiments, the specific targeting of short hairpin RNAs via lentiviruses successfully induced the knockdown of FBXL19, resulting in notable inhibition of the proliferation, migration, and invasion of HCC cells. Furthermore, FBXL19 downregulation resulted in significant induction of G0/G1 phase cell cycle arrest. Importantly, FBXL19 knockdown inhibited tumour malignant behaviour primarily by inactivating extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinases. In conclusion, this study revealed that FBXL19 was upregulated in patients with HCC, and that its expression was negatively correlated with prognosis. Thus, FBXL19 displays oncogenic properties in HCC by activating mitogen-activated protein kinase signalling.
