UPF1 inhibits the hepatocellular carcinoma progression by targeting long non-coding RNA UCA1

Abstract

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. However, the molecular mechanism underlying HCC carcinogenesis remains to be further elucidated. Up-frameshift protein 1 (UPF1) is a RNA/DNA-dependent ATPase and ATP-dependent RNA helicase. Here, we explored the expression and function of UPF1 in HCC. In this study, we demonstrated that UPF1 expression was significantly reduced in hepatocellular carcinoma (HCC) tissues compared with the adjacent normal tissues. And further functional assays revealed that knockdown of UPF1 promoted HCC cells growth and invasion. Furthermore, we found that UPF1 could bind to long non-coding RNA urothelial cancer associated 1 (UCA1) and was negatively correlated with UCA1. UCA1 expression also affected HCC growth and invasion. Knockdown of UCA1 ameliorated the effect of UPF1 knock down on HCC growth and invasion. Knockdown of UPF1 enhances glycolysis in HCC. Taken together, our results provided new insights for finding novel therapeutic targets for hepatocellular carcinoma progression.

Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma

“…The regulatory ncRNAs are broadly subcategorized into microRNAs (miRNAs, 18-25 nt), small interfering RNAs (siRNAs, <200 nt), piwi-interacting RNAs (piRNAs, <200 nt), and long noncoding RNAs (lncRNAs, >200 nt) [11]. Emerging studies on regulatory ncRNAs have shown their role as biomarkers or physiological regulators in many types of cancers, such as breast cancer, osteosarcoma, lung cancer, hepatocellular carcinoma, cervical cancer, bladder cancer [12][13][14][15][16]. Moreover, there have been increased investigations into the role of ncRNAs in ESCC [17][18][19].…”

UPF1 Promotes Chemoresistance to Oxaliplatin Through Maintenance of Stemness by Increasing Phosphorylated TOP2A in Colorectal Cancer.

“…Feng Q et al reported that UPF1 acted as an E3 ubiquitin ligase to repress human skeletal muscle differentiation [29]. In addition, UPF1 is proved to dysregulate in multiple tumors and in uence carcinogenesis [13][14][15]. However, there is lack of detailed study of UPF1 in CRC.…”

“…UPF1 is commonly mutated in pancreatic adenosquamous carcinoma (ASC) and there is little or no UPF1 expression in many ASC tumors compared to adjacent normal tissue [13]. It is revealed that UPF1 is downregulated in hepatocellular carcinoma and inhibits the tumor progression [14,15]. However, the role of UPF1 in oxaliplatin resistance in CRC remains unclear.…”

Interaction Between LncRNA and UPF1 in Tumors

“…UPF1 binds to MALAT1 and promotes its degradation, thereby inhibiting the expression of MALAT1 in gastric cancer ( Li et al, 2017 ). In HCC, the expression of UPF1 is decreased, and silencing of UPF1 promotes the growth and invasion of HCC cells ( Zhou et al, 2019 ). Knockdown of UPF1 in HCC cells increases the expression of UCA1 ( Zhou et al, 2019 ).…”