Long Non-Coding RNA LINC00346 Promotes Hepatocellular Carcinoma Progression Through the Wnt/β-Catenin Signaling Pathway

Background: Long non-coding RNAs (lncRNAs) have received increased attention to act as important regulators in cancer progression. However, a large fraction of them have not been characterized and the functional mechanism of LINC00346 in hepatocellular carcinoma (HCC) remains unclear. Methods: The role of LINC00346 in HCC was investigated in vitro and in vivo. The interaction between LINC00346, miR-542-3p, and WDR18 was identified using luciferase activity assays, RT-qPCR, and western blotting. Loss (or gain)-of-function experiments were performed to investigate the biological roles of LINC00346, miR-542-3p, and WDR18 on cell viability, proliferation, migration, invasion, and cell apoptosis. Findings: We demonstrated that LINC00346 was upregulated in HCC, and LINC00346 can promote cell viability, proliferation, migration and invasion, but repress apoptosis of HCC cells. Furthermore, we revealed that LINC00346 regulates WDR18 expression via competitive binding with miR-542-3p, which was downregulated in HCC and acted as a tumor suppressor that can inhibite cell viability, proliferation, migration and invasion, but promote apoptosis of HCC cells, whereas WDR18 was upregulated in HCC and functioned as an oncogenic role in HCC. Moreover, further functional mechanism investigation illustrated that WDR18 activates the Wnt/β-catenin signaling pathway and downstream moleculars. Finally, we found that LINC00346 acts as ceRNA via competitively sponging miR-542-3p, enhancing the expression of WDR18 and activating the Wnt/β-catenin signaling pathway in HCC. Interpretation: Our results uncover a potential mechanism to understand the oncogenic role of LINC00346 and provide profoundly a prospective biomarker and potential therapeutic target in HCC. Funding: This work was supported by the National Natural Science Foundation of China (No.81760427). Declaration of Interest: The authors declare that they have no competing financial interests. Ethical Approval: The process was approved by Ethics Committee of The Second Affiliated Hospital of Nanchang University, and all patients were informed and written informed consent.