Lv Yong, Xie Xiaolong, Zou Guoyou, Kong Meng, Yang Jiayin, Chen Jing, Xiang Bo
Department of Pediatric Surgery and Laboratory of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of General Surgery, People's Hospital of Tibet Autonomous Region, Tibet 850000, China.
Precis Clin Med. 2023 Oct 20;6(4):pbad027. doi: 10.1093/pcmedi/pbad027. eCollection 2023 Dec.
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 microRNAs (miRNAs) and the progression of tumor metastasis in HB.
The study utilized weighted gene co-expression network analysis (WGCNA) to analyze a miRNA microarray dataset of HB. The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR. The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays. The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated . Furthermore, a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB.
We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines. Overexpression of miR-181b enhanced scratch healing, cell migration, and invasion abilities , as well as enhancing HB lung metastasis potential . Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2 (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 and JAK2/STAT5 signaling pathways. The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells.
Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.
肝母细胞瘤（HB）是一种主要发生于儿童的恶性肝肿瘤，肿瘤转移是影响患者预后不良的主要原因之一。导致HB转移的确切分子机制仍未完全明确。然而，有证据表明，微小RNA（miRNA）失调与HB肿瘤转移进展之间存在关联。
本研究利用加权基因共表达网络分析（WGCNA）对HB的miRNA微阵列数据集进行分析。采用定量实时PCR检测miR-181b-5p在HB组织和细胞中的表达。通过划痕实验和Transwell实验评估miR-181b-5p对HB转移能力的影响。评估外源性表达miR-181b对HB细胞转移表型的影响。此外，进行荧光素酶报告基因实验以验证miR-181b-5p在HB中的潜在靶标。
我们发现miR-181b-5p在HB组织和HB细胞系中高表达。miR-181b的过表达增强了划痕愈合、细胞迁移和侵袭能力，以及增强了HB的肺转移潜能。双荧光素酶报告基因实验表明，细胞因子信号转导抑制因子2（SOCS2）是miR-181b的直接靶标。miR-181b的过表达导致SOCS2表达受到抑制，随后激活上皮-间质转化和JAK2/STAT5信号通路。挽救实验表明，SOCS2的过表达减弱了miR-181b对HB细胞的影响。
我们的研究表明，miR-181b通过靶向SOCS2促进HB转移，可能是HB的潜在治疗靶点。
