研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

miR-181b-5p/SOCS2/JAK2/STAT5轴促进肝母细胞瘤的转移。

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

发表日期:2023 Dec
作者: Yong Lv, Xiaolong Xie, Guoyou Zou, Meng Kong, Jiayin Yang, Jing Chen, Bo Xiang
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

肝母细胞瘤(HB)是一种主要见于儿童的恶性肝脏肿瘤,肿瘤转移是患者预后不良的主要原因之一。 HB 转移的精确分子机制仍不完全清楚。然而,有证据表明 HB 中 microRNA (miRNA) 的失调与肿瘤转移的进展之间存在联系。该研究利用加权基因共表达网络分析 (WGCNA) 来分析 HB 的 miRNA 微阵列数据集。采用实时定量PCR检测HB组织和细胞中miR-181b-5p的表达。通过划痕和Transwell实验评估miR-181b-5p对HB转移能力的影响。体内评估外源表达 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测定以验证 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 的过表达可增强体外划痕愈合、细胞迁移和侵袭能力,并增强体内 HB 肺转移潜力。双荧光素酶报告基因检测显示细胞因子信号传导抑制因子 2 (SOCS2) 是 miR-181b 的直接靶标。 miR-181b 的过表达导致 SOCS2 表达抑制,随后激活上皮间质转化和 JAK2/STAT5 信号通路。拯救实验表明SOCS2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。©作者2023。已发表牛津大学出版社代表华西医学院
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 in vivo. 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 in vitro, as well as enhancing HB lung metastasis potential in vivo. 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.© The Author(s) 2023. Published by Oxford University Press on behalf of the West China School of Medicine & West China Hospital of Sichuan University.