Abstract
Objective To explore the potential biological roles of long noncoding RNA (lncRNA) RNCR3 in human hepatocellular carcinoma (HCC). Methods First, the expression of RNCR3 was detected by qRT-PCR. Then, in vitro experiments were performed to investigate the effects of RNCR3 on the proliferation, cell cycle, migration, and invasion of HCC cells, while the effects of RNCR3 on HCC tumor growth and metastasis were investigated using in vivo experiments. Finally, western blot was used to study the activation of the Akt/GSK3β signaling pathway. Results RNCR3 was highly expressed in both HCC tissues and cells, and the expression of RNCR3 was closely related to tumor size, tumor number, TNM stage, and overall survival time. In vitro, RNCR3 served as an oncogene to promote cell proliferation, migration, and invasion, and in vivo, RNCR3 promoted the growth and metastasis of HCC tumors. In terms of mechanism, RNCR3 induced the phosphorylation of Akt (thr308 and ser473) and GSK3β (ser9) but decreased the expression of GSK3β, which activated the Akt/GSK3β signaling pathway. Conclusion The high expression of lncRNA RNCR3 in HCC can promote the proliferation, migration, invasion, growth, and metastasis of HCC by activating the NF-κB signaling pathway.
Highlights
Hepatocellular carcinoma (HCC) accounts for nearly 80% of all primary liver cancers, ranking third among cancer-related deaths, and a large number of patients die from HCC every year globally [1, 2]
Surgical resection is still the main choice for patients with resectable HCC, but due to the rapid tumor progression and intrahepatic and extrahepatic metastasis, the postoperative tumor recurrence rate is still very high, which leads to a poor prognosis [3]. erefore, preventing the progress and metastasis of hepatocellular carcinoma is the most important task at present, and exploring the molecular mechanism of the occurrence and development of liver cancer is of great significance for finding new therapeutic targets
The expression of RNCR3 in the HCC cell line was significantly higher than that of the human normal liver cell line (Figure 1(c)). ese results indicated that RNCR3 was highly expressed in HCC. e expression of Long noncoding RNA (lncRNA) LINC01554, which has been reported in HCC, was tested as a positive control, and it was found that the LINC01554 expression was downregulated in HCC tissues (Figure 1(d))
Summary
Hepatocellular carcinoma (HCC) accounts for nearly 80% of all primary liver cancers, ranking third among cancer-related deaths, and a large number of patients die from HCC every year globally [1, 2]. Erefore, preventing the progress and metastasis of hepatocellular carcinoma is the most important task at present, and exploring the molecular mechanism of the occurrence and development of liver cancer is of great significance for finding new therapeutic targets. It has been reported that lncRNAs are involved in various cellular processes including cell proliferation, apoptosis, cell cycle, and invasion, and more and more evidence shows that the abnormal expression of lncRNAs that served as oncogenes or tumor suppressor genes is related to the occurrence and development of various cancers [5, 6]. The expression of LINC01554 in HCC is significantly downregulated, and its expression has a significant relationship with the tumor size, multiple lesions, TNM stage, tumor recurrence rate, and long-term survival rate of liver cancer patients [7]. It is reported that LINC00467 can promote the proliferation and invasion of HCC cells through miR-509-3p/PDGFRA, inhibit cell apoptosis, and contribute to Axitinib resistance of hepatocellular carcinoma, which indicates that
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