MicroRNA-552 promotes hepatocellular carcinoma progression by downregulating WIF1

Abstract

MicroRNAs (miRNAs/miRs) are involved in the metastasis of hepatocellular carcinoma (HCC). In the present study, it was demonstrated that miR-552 was upregulated in HCC tissues. High miR-552 expression was associated with malignant clinicopathological features and decreased survival rates. The in vitro results indicated that miR-552 overexpression promoted migration, invasion and epithelial-mesenchymal transition in Hep3B cells. However, the knockdown of miR-552 inhibited its oncogenic roles in Huh-7 cells. Additionally, Wnt inhibitory factor 1 (WIF1) was demonstrated to be a direct target of miR-552 in Hep3B and Huh-7 cells. Additional experiments identified that miR-552 promotes β-catenin expression by increasing the phosphorylation of GSK3β at Ser9. In conclusion, the results suggested that miR-552 may promote HCC progression by blocking WIF1-mediated GSK3β dephosphorylation. miR-552 may be a biomarker for predicting the outcomes of patients with HCC.

miR-552: an important post-transcriptional regulator that affects human cancer

“…Comparing miR-552 expression in 158 pairs of colon cancer (CC) adenocarcinoma tissues with proficient DNA mismatch repair (pMMR) and adjacent tissues found that miR-552 expression was significantly associated with CC risk [20]. In liver cancer (HCC), Qu W et al detected the expression levels of miR-552 in 81 pairs of HCC tissues and adjacent non-tumor tissues and found that miR-552 expression levels in HCC tissues were increased [3], which was found in the other two independent studies [26,27]. Han T et al found that miR-552 was overexpressed in liver tumor-initiating cells (T-ICs) [28].…”

“…In HCC cells, miR-552 increased the expression level of E-cadherin and down-regulated the expression of N-cadherin and vimentin by down-regulating the expression of AJAP1 [3]. In the HCC HIF3B cell line, miR-552 could down-regulate WIF1 expression, increase the effect of E-cadherin, and promote the EMT pathway [27]. miR-552 can target RUNX3 by inhibiting miR-186/E-cadherin/ EMT pathway, thereby promoting cell migration and invasion of HCC cells [26,57].…”

“…Abnormal Wnt/β-catenin pathway may lead to cell proliferation and malignant transformation [43,44], of which WIF1 plays a tumor-suppressive role by directly binding to Wnt protein [45]. In HCC, miR-552 binds to the 3'-UTR of WIF1 mRNA to form an RNA-induced silencing complex (RISC), which inactivates the Wnt/β-catenin signaling pathway to promote cell proliferation [27]. HER2 belongs to the receptor tyrosine kinase of the epidermal growth factor receptor (EGFR) family [46].…”

“…Epithelial-mesenchymal transition (EMT) is an important biological process for epithelial cellsderived malignant tumor cells to acquire the ability to migrate and invade [58] (Figure 3). MiR-552 can promote the development of EMT by targeting AJAP1 [3], WIF1 [27], RUNX3 [26], and FOXO3 [33]. In HCC cells, miR-552 increased the expression level of E-cadherin and down-regulated the expression of N-cadherin and vimentin by down-regulating the expression of AJAP1 [3].…”

“…In HCC cells, miR-552 overexpression can target the inhibition of AJAP1, which promotes the migration, invasion, and EMT of HCC cells, and is associated with poor prognosis in HCC patients [3]. The high expression of miR-552 in HCC is associated with malignant clinicopathological features and decreased survival [27]. High levels of miR-552 are associated with poor disease-free survival (DFS) and overall survival in patients [28].…”