| 李江斌,何 丽,董 瑞,徐 岩,鲁建国.miR-369-3p靶向FGF9信号通路调控肝癌细胞增殖与侵袭[J].现代生物医学进展英文版,2020,(9):1601-1608. |
| miR-369-3p靶向FGF9信号通路调控肝癌细胞增殖与侵袭 |
| Regulation of Hepatocellular Carcinoma Cell Proliferation and Invasion by miR-369-3p Via Targeting FGF9 Signaling Pathway |
| Received:October 23, 2019 Revised:November 18, 2019 |
| DOI：10.13241/j.cnki.pmb.2020.09.001 |
| 中文关键词: 肝癌 miR-369-3p 增殖 侵袭 纤维母细胞生长因子9 转录后调控 |
| 英文关键词: Hepatocellular carcinoma (HCC) miR-369-3p Proliferation Invasion Fibroblast growth factor 9 (FGF9) Posttranscr- iptional regulation |
| 基金项目:国家自然科学基金项目（31271248） |
| Author Name | Affiliation | E-mail | | LI Jiang-bin | Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China | fengkai_2014@126.com | | HE Li | Department of Infectious Disease, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China | | | DONG Rui | Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China | | | XU Yan | Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China | | | LU Jian-guo | Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China | |
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| 中文摘要: |
| 摘要 目的：阐明脂代谢相关miR-369-3p在肝癌（hepatocellular carcinoma, HCC）病理组织中的表达特征及其与临床预后的相关性，解析miR-369-3p在HCC细胞中的作用性质及相应分子机理。方法：实时定量PCR法检测miR-369-3p在HCC病理组织和细胞中的表达变化，并通过Spearman's法分析miR-369-3p表达水平与临床病理资料相关性；CCK-8检测、Transwell穿透小室实验和裸鼠荷瘤实验检测敲低内源性miR-369-3p表达后对HCC细胞增殖和侵袭性的影响作用；利用生物信息学分析、瞬时转染、定点突变和荧光素酶报告基因活性检测分析miR-369-3p对纤维母细胞生长因子9（fibroblast growth factor 9，FGF9）的转录后调控作用。结果：miR-369-3p在HCC病理组织（n=68）和细胞中异常低表达，且此低表达趋势与HCC患者预后呈显著负相关关系（x2=6.907，P=0.0086）；敲低内源性miR-369-3p可显著促进HCC细胞的增殖、侵袭性；参与调控这一抑瘤效应的关键分子机制可能是miR-369-3p与FGF9的3'-UTR区直接结合，在转录后水平抑制FGF9 mRNA的稳定性，进而抑制后者表达水平。结论： miR-369-3p可通过靶向FGF9信号在转录后调控水平负性调控肝癌细胞增殖和侵袭过程，在肝癌发生和进展过程中发挥关键抑癌作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the expression and clinical relevance of miR-369-3p, a lipid metabolism-related miRNA, in hepatocellular carcinoma (HCC) tissues, and to reveal the functional details and corresponding molecular basis of miR-369-3p in HCC cells. Methods: Expression levels of miR-369-3p were determined in HCC cell lines and surgically removed HCC tissues using RT-qPCR analysis. Effects of miR-369-3p manipulation on HCC progression were evaluated using cell proliferation, cell invasion and xenograft assays. Finally, bioinformatics analysis, transient transfection, site-directed mutagenesis and luciferase reporter assay were incorporated to determine the potential regulation of fibroblast growth factor 9 (FGF9) expression by miR-369-3p. Results: miR-369-3p expression was markedly down-regulated in surgical HCC specimens (n=68), and this down-regulation trend correlated well to disease progression and predicted a poor prognosis in HCC patients (χ2=6.907, P=0.0086). Functionally, miR-369-3p depleted-cells had significantly higher proliferative, invasive and in vivo tumor formation potential, compared to Ctrl cells. One major mechanism accounting for the above-mentioned tumor suppressor effects of miR-369-3p is that miR-369-3p may inhibit the FGF9 expression at the posttranscriptional level via directly binding to its 3'-UTR. Conclusion: miR-369-3p may negatively regulate the proliferation and invasion of HCC cells by directly targeting the FGF9 signaling pathway at the posttranscriptional level. Collectively, miR-369-3p may function as a potent tumor suppressor during the development and progression of HCC. |
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