OncoTargets and Therapy (Jun 2021)
m6A-Induced LncRNA MEG3 Suppresses the Proliferation, Migration and Invasion of Hepatocellular Carcinoma Cell Through miR-544b/BTG2 Signaling
Abstract
Jian Wu,* Runhua Pang,* Minan Li, Bin Chen, Junhai Huang, Yaqing Zhu The Third Department of Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaqing ZhuThe Third Department of Surgery, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Airport Road, Guangzhou, Guangdong, 510405, People’s Republic of ChinaEmail [email protected]: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Long non-coding RNA plays an important role in the development of HCC. This study analyzed the impact of MEG3 on malignant behavior of HCC and explored its possible molecular mechanism.Methods: Expression of MEG3 in HCC tissues and cell lines was measured by qRT-PCR. Transfection efficiency of MEG3 was verified by qRT-PCR. Cell proliferation, transwell migration, invasion and cell cloning assays were used to detect the effect of MEG3 on the proliferation, migration and invasion ability of HCC cells. The bioinformatics analysis was applied to predict the binding between miR-544b and MEG3 as well as BTG2. Luciferase reporter assay was performed to verify their interaction. Finally, the m6A modification of MEG3 by METTL3 was identified through RIP experiments.Results: MEG3 was lowly expressed in HCC tissues and cells. Overexpression of MEG3 inhibits the proliferation, migration and invasion of HCC cells. MiR-544b can be sponged by MEG3, and overexpression of miR-544b reverses the anti-cancer effect of MEG3. We further confirmed that BTG2 gene is the target gene of miR-544b. Epigenetic studies have shown that METTL3-mediated N6-methyladenosine modification led to MEG3 downregulation.Conclusion: In HCC, MEG3 and BTG2 are lowly expressed while miR-544b is highly expressed. MEG3 regulates the expression of BTG2 through miR-544b, thus affecting the malignant behavior of HCC. METTL3 regulates the m6A modification of MEG3 and its expression. This study clarified the role of MEG3/miR-544b/BTG2 axis in HCC and also provided new targets for HCC research.Keywords: lncRNA MEG3, miR-544b, HCC, N6-methyladenosine, BTG2
