Lncrna HOXD-AS1 Functions As A Cerna To Promote Hepatocellular Carcinoma Metastasis In Zebrafish Xenograft Models

Recent studies have suggested that long noncoding RNA (lncRNA) HOXD cluster antisense RNA 1 (HOXD-AS1) plays an important role in hepatocellular carcinoma (HCC) metastasis as a competing endogenous RNA (ceRNA). However, there is no in vivo evidence supporting this. Employing zebrafish HCC xenograft as an in vivo metastasis model, we aim to verify the role of ceRNA network of HOXD-AS1 in HCC metastasis. The quantitative reverse transcription PCR (qRT-PCR) assay was used to assess the expression level of HOXD-AS1 in HCC cell lines. Knockdown of HOXD-AS1 or miR-130a-3p was performed by transfecting small interfering RNA (siRNA) or microRNA (miRNA) inhibitor, respectively. The proliferation and migration of HCC cells in vitro were analyzed by CCK-8 and transwell assays. The growth and metastasis of HCC cells in vivo were assessed by zebrafish xenograft models. We verified that HOXD-AS1 was overexpressed in all tested HCC cell lines compared to the normal hepatic cells. Silence of HOXD-AS1 suppressed cell proliferation and migration in Hep3B and Huh7 HCC cell lines, respectively. In zebrafish xenograft models, knockdown of HOXD-AS1 also reduced the growth and metastasis of the two HCC cells. Downregulation of miR-130a-3p rescued the metastasis which inhibited by silence of HOXD-AS1 in vitro and in vivo . Moreover, HOXD-AS1 knockdown enhanced the inhibition effect of oxaliplatin for HCC progression in vitro and in vivo . Our study demonstrates the pro-metastastic role of the HOXD-AS1/miR-130a-3p ceRNA network in HCC cells, and provides evidence that HOXD-AS1 may serve as a biomarker and potential therapeutic target for HCC metastasis.