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. 2019 Nov 7:11:9371-9378.
doi: 10.2147/CMAR.S220434. eCollection 2019.

LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/β-Catenin Pathway

Xiaoxiao Yao #  1 , Guangqiang You #  1 , Chen Zhou  2 , Dan Zhang  1
Affiliations

LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/β-Catenin Pathway

Xiaoxiao Yao et al. Cancer Manag Res. .

Retraction in

Abstract

Background: To date, although several long noncoding RNAs (lncRNAs) are reported to regulate hepatocellular carcinoma (HCC) development, their relationship still remains elusive. ASB16-AS1 is a poorly researched novel lncRNA. We aimed to investigate its function in HCC progression.

Methods: qRT-PCR and in situ hybridization (ISH) were used to analyze ASB16-AS1 expression in HCC tissues. CCK8, Edu incorporation and colony formation were used to determine cell proliferation. Transwell assay was used to examine migration and invasion. Luciferase reporter assay was used to analyze the interactions among ASB16-AS1, miR-1827 and FZD4.

Results: Bioinformatics analysis identified ASB16-AS1 was overexpressed in HCC tissues, which was further validated by qRT-PCR and in situ hybridization (ISH). Besides, ASB16-AS1 was demonstrated to be a potential indicator for HCC prognosis. Functional studies showed ASB16-AS1 knockdown attenuated proliferation, migration and invasion of HCC cells. Mechanistically, ASB16-AS1 directly interacted with miR-1827 and promoted FZD4 expression by sponging miR-1827. Overexpressed FZD4 eventually activated Wnt/β-catenin pathway and contributed to HCC progression.

Conclusion: Our work is the first to identify ASB16-AS1 as an oncogene that enhances HCC progression by modulating miR-1827/FZD4/Wnt/β-catenin pathways.

Keywords: ASB16-AS1; FZD4; HCC; lncRNA; miR-1827.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Upregulated ASB16-AS1 correlates with poor prognosis in HCC. (A) Analysis of differentially expressed lncRNAs between HCC and control tissues using Cancer RNA-seq Nexus tool (http://syslab4.nchu.edu.tw/). (B) ASB16-AS1 transcripts were indicated according to Cancer RNA-seq Nexus tool. (C) ASB16-AS1 expression was analyzed using GEPIA tool (http://gepia.cancer-pku.cn/). (D) qRT-PCR analysis of ASB16-AS1 expression in 51 pairs of HCC and adjacent normal tissues. (E) In situ hybridization (ISH) for ASB16-AS1 expression in HCC and paired normal tissues. (F) Expression of ASB16-AS1 in different stages of HCC tissues. (G) Overall survival rate was analyzed based on ASB16-AS1 expression. (H) Disease-free survival rate was analyzed in HCC patients using GEPIA tool according to ASB16-AS1 expression. *p<0.05.
Figure 2
Figure 2
Effects of ASB16-AS1 knockdown on HCC cells. (A) Expression patterns of ASB16-AS1 in HCC cell lines. (B) shRNA-caused knockdown of ASB16-AS1 in Huh7 and Hep3B cells was validated by qRT-PCR. (C–E) Cell proliferation was evaluated by CCK8, EdU incorporation, and colony formation assays. (F and G) Transwell assay for analysis of cell migration and invasion. *p<0.05.
Figure 3
Figure 3
ASB16-AS1 regulates miR-1827/FZD4/Wnt/β-catenin pathway. (A) Strategies for construction of wild-type (WT) or mutant (MUT) ASB16-AS1and FZD4 luciferase reporter vectors. (B and C) Luciferase reporter assay using ASB16-AS1and FZD4 luciferase reporter vectors in Huh7 cells. (D) Pulldown assay indicated miR-1827 interacted with ASB16-AS1. (E) RIP assay showed miR-1827 interacted with FZD4 mRNA in Huh7 cells. (F) ASB16-AS1 knockdown increased miR-1827 level. (G) Expression of FZD4 was tested after transfection with indicated vectors. (H) Target genes (CCND1, CCND2, MYC and SOX4) of Wnt/β-catenin pathway were analyzed by qRT-PCR in Huh7 cells. (I) FZD4 expression was analyzed using UALCAN tool (http://ualcan.path.uab.edu/analysis.html). (J) Relative expression of FZD4 was analyzed by qRT-PCR in HCC tissues. *p<0.05.
Figure 4
Figure 4
FZD4 rescues the effects of ASB16-AS1 knockdown. (A–C) Cell proliferation was measured by using CCK8, EdU incorporation and colony formation assays. (D and E) Transwell assay was performed to determine migration and invasion. *p<0.05.
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