miR-155-5p modulates malignant behaviors of hepatocellular carcinoma by directly targeting CTHRC1 and indirectly regulating GSK-3β-involved Wnt/β-catenin signaling

Gang Chen; Dongdong Wang; Xiongqi Zhao; Jun Cao; Yingpeng Zhao; Fan Wang; Jianhua Bai; Ding Luo; Li Li

doi:10.1186/s12935-017-0469-8

miR-155-5p modulates malignant behaviors of hepatocellular carcinoma by directly targeting CTHRC1 and indirectly regulating GSK-3β-involved Wnt/β-catenin signaling

Cancer Cell Int. 2017 Dec 8:17:118. doi: 10.1186/s12935-017-0469-8. eCollection 2017.

Authors

Gang Chen¹, Dongdong Wang¹, Xiongqi Zhao¹, Jun Cao¹, Yingpeng Zhao¹, Fan Wang¹, Jianhua Bai¹, Ding Luo¹, Li Li¹

Affiliation

¹ Department of Hepatobiliary Surgery, First People's Hospital of Kunming City, No. 504 Qinnian Road, Kunming, 650034 Yunnan China.

Abstract

Background: Hepatocellular carcinoma (HCC) remains one of the most lethal cancers. MicroRNA-155 (miR-155) and collagen triple helix repeat containing 1 (CTHRC1) were found to be involved in hepatocarcinogenesis, but their detailed functions in HCC are unclear. Here, we aimed to investigate the underlying role of miR-155-5p and CTHRC1 in HCC.

Methods: miR-155-5p and CTHRC1 expression levels were detected by qRT-PCR, IHC and WB in HCC patients and cell lines. Dual-luciferase assay, qRT-PCR and WB were used to validate the target interaction between miR-155-5p and CTHRC1. Biological behaviors, including apoptosis, cell cycle progression, and cell proliferation, invasion and migration, were measured by flow cytometry, CCK-8 assay and Transwell tests. A xenograft model was established to examine the effects of miR-155-5p and CTHRC1 on tumor formation. WB was finally utilized to identify the role of GSK-3β-involved Wnt/β-catenin signaling in HCC growth and metastasis.

Results: Our results showed that miR-155-5p and CTHRC1 were down-regulated and up-regulated, respectively, in HCC patients and cell lines. Dual-luciferase assay verified that CTHRC1 was the direct target of miR-155-5p. Moreover, elevated miR-155-5p expression promoted apoptosis but suppressed cell cycle progression and cell proliferation, invasion and migration in vitro and facilitated tumor formation in vivo; elevated CTHRC1 expression abolished these biological effects. Additionally, miR-155-5p overexpression increased metastasis- and anti-apoptosis-related protein expression and decreased pro-apoptosis-related protein expression, while forced CTHRC1 expression conserved the expression of these proteins.

Conclusion: Altogether, our data suggested that miR-155-5p modulated the malignant behaviors of HCC by targeting CTHRC1 and regulating GSK-3β-involved Wnt/β-catenin signaling; thereby, miR-155-5p and CTHRC1 might be promising therapeutic targets for HCC patients.

Keywords: Collagen triple helix repeat containing 1 (CTHRC1); GSK-3β-involved Wnt/β-catenin signaling; Hepatocellular carcinoma (HCC); Malignant behaviors; microRNA-155-5p (miR-155-5p).