LncRNA DDX11-AS1 accelerates hepatocellular carcinoma progression via the miR-195-5p/MACC1 pathway

Introduction and aim: Long non-coding RNA (lncRNA) has been shown to be a vital regulator of cancer progression, including hepatocellular carcinoma (HCC). However, the role of DEAD/H box protein 11 antisense RNA 1 (DDX11-AS1) in HCC remains to be further studied. Material and Methods: The expression levels of DDX11-AS1, miR-195-5p and metastasis-associated in colon cancer-1 (MACC1) were determined by quantitative real-time PCR (qRT-PCR). Cell counting kit-8 (CCK-8), transwell and apoptosis determination assays were used to evaluate cell proliferation, migration, invasion and apoptosis, respectively. Mice xenograft models were constructed to verify the effect of DDX11-AS1 on HCC tumor growth in vivo. Furthermore, lactate production, glucose consumption, ATP level and glucose uptake were detected to assess cell glucose metabolism. The interactions among DDX11-AS1, miR-195-5p and MACC1 were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Moreover, western blot (WB) analysis was performed to evaluate the protein levels. Results: DDX11-AS1 was upregulated in HCC tissues and cells, and its silencing could inhibit HCC cell proliferation, migration, invasion and glucose metabolism, and promote apoptosis in vitro. Also, DDX11AS1 knockdown reduced HCC tumor growth in vivo. Besides, DDX11-AS1 could interact with miR-195-5p, and miR-195-5p inhibitor reversed the inhibitory effect of silenced DDX11-AS1 on HCC cell progression. In addition, MACC1 was a target of miR-195-5p, and its overexpression reversed the suppression effect of miR-195-5p on HCC cell progression. Conclusion: Our data revealed that DDX11-AS1 could act as an oncogenic regulator in HCC, providing a potential therapeutic target for HCC treatment. (C) 2020 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espaa, S.L.U. This is an open access article under the CC BY-NC-ND license.

Automated summary

In this study, it was found that DDX11-AS1 is upregulated in HCC, and its silencing can inhibit HCC cell proliferation, migration, invasion, and glucose metabolism while promoting apoptosis. Additionally, DDX11-AS1 interacts with miR-195-5p and MACC1, suggesting it may serve as a potential therapeutic target for HCC.