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Interference of miR-107 with Atg12 is Inhibited by HULC to Promote Metastasis of Hepatocellular Carcinoma
28 Pages Posted: 8 Jan 2019
More...Abstract
Introduction: We attempted to determine the role of HULC and miR-107 on autophagy and invasion of HCC.
Methods: The relationship of HULC, miR-107, Atg12 and autophagy were showed by cell lines. HULC and miR-107 were regulated by siRNAs. Autophagy was visualized using an mRFP-GFP-LC3 adenovirus vector. Proteins were detected by Western blot analysis. The invasiveness of HCC was assessed by transwell assay.
Results: In cell lines, HULC siRNA reduced the level of autophagy. The impact of HULC siRNA on invasion can be reversed by activating autophagy in cell lines. Further studies on HULC and autophagy were conducted. An interacting sequence between HULC and miR-107, as well as miR-107 and Atg12, was predicted by software. The relationship of each pair of molecules was confirmed by Luciferase reporter assays or supported by negative correlations of expressions in cell lines. The similar impacts of miR-107 on autophagy and invasion as HULC siRNA were proved in cell lines. HULC/miR-107 regulated invasion can also be reversed by Atg12 siRNA. The changes of miR-107, Atg12, EMT and autophagy in transplanted tumors of mouse models also complied with the results in cell lines.
Conclusions: The HULC/miR-107/Atg12 axis promotes autophagy and metastasis of HCC.
Funding Statement: This work was supported by National Scientific and Technological Projects for Major Infectious Diseases (2017ZX10203205-003-004), National Natural Science Foundation of China (81700556), National Major Scientific and Technological Special Project for Significant New Drugs Development (2014ZX09101005004).
Declaration of Interests: The authors have declared that no conflict of interest exists.
Ethics Approval Statement: Animal experiments were conducted with the approval by the ethics committee of Beijing Friendship Hospital.
Keywords: HULC; miR-107; Atg12; autophagy; HCC
Suggested Citation: Suggested Citation