miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma

Abstract

Introduction Hepatoblastoma (HB) is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients. The precise molecular mechanisms responsible for HB metastasis remain incompletely understood. However, there is evidence suggesting a connection between the dysregulation of miRNAs and the progression of tumor metastasis in HB. Methods The study utilized weighted gene co-expression network analysis (WGCNA) to analyze a microRNA microarray dataset of hepatoblastoma. The expression of miR-181b-5p in hepatoblastoma tissues and cells was detected using qRT-PCR. The impact of miR-181b-5p on the metastatic capacity of hepatoblastoma (HB) was evaluated through scratch and Transwell assays. The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo. Furthermore, a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB. Results We found that miR-181b-5p was highly expressed in hepatoblastoma tissues and HB cell lines. Overexpression of miR-181b enhanced scratch healing, cell migration and invasion abilities in vitro, as well as enhanced HB lung metastasis potential in vivo. Dual-luciferase reporter assays showed that SOCS2 was a direct target of miR-181b. The overexpression of miR-181b resulted in the suppression of SOCS2 expression, subsequently activating the epithelial-mesenchymal transition (EMT) and JAK2/STAT5 signaling pathways. The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells. Conclusion Our study showed that miR-181b promotes hepatoblastoma metastasis by targeting SOCS2 and may be a potential therapeutic target for hepatoblastoma.

Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma

“…In addition, CEBPA, IRAK1, MAP2K2, GP1 , and CD63 were also highly expressed in HERV-K high tumors. In HERV-K low tumors there was significantly higher expression of EPCAM , a well-established epithelial gene, and SOCS2 , a suppressor of cytokine-induced JAK/STAT signaling that has been implicated in the regulation of epithelial-mesenchymal transition in cancers (31, 32). In the vessels of HERV-K high tumors (Fig.…”

“…This is further supported by the increased expression of SOCS2 in HERV-K low tumors. Increased SOCS2 expression has been shown to inhibit EMT, and the downregulation of SOCS2 has been associated with EMT activation, increased metastasis, and worse overall prognosis in HCC and other cancers (31, 32, 40). In both LINE1 high and HERV-K high tumors, members of the Cancer Testis Antigen (CTA) group (SSX1 and MAGEC2) were highly expressed.…”