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目的 探讨跨膜蛋白147(TMEM147)在肝细胞癌(HCC)中的表达特征、临床意义及其调控肿瘤进展的分子机制。方法 利用癌症基因组图谱(TCGA)数据库、免疫组织化学染色(IHC)、实时荧光定量PCR(qRT-PCR)、Western blot(WB)分析TMEM147在HCC中的表达及预后价值；利用小干扰RNA和过表达质粒调控TMEM147表达，并结合CCK-8、EdU、Transwell、划痕实验和裸鼠皮下移植瘤模型评估其对HCC细胞增殖及转移的影响；通过转录组测序(RNA-seq)及磷脂酰肌醇3-激酶/蛋白激酶B信号通路(PI3K/AKT)通路抑制剂(LY294002)探究TMEM147影响肝癌细胞增殖转移的分子机制。结果 TCGA数据分析、IHC、qRT-PCR以及WB实验证实HCC中TMEM147表达上调(P<0.05),且高表达患者总生存期(OS)明显缩短(P<0.001),多因素Cox分析结果显示TMEM147是影响患者预后的独立危险因素(P=0.01);敲低TMEM147可抑制HCC细胞增殖和转移，而过表达则促进上述表型(P<0.05);在动物模型中，TMEM147过表达组肿瘤体质量和体积增加(P<0.05);RNA-seq结果表明，TMEM147通过激活PI3K/AKT信号通路驱动HCC进展，而PI3K抑制剂可逆转TMEM147的促癌效应。结论 TMEM147在HCC中高表达且与不良预后密切相关，其通过激活PI3K/AKT通路促进肝肿瘤细胞增殖及转移，可作为HCC潜在的预后标志物和治疗靶点。
Abstract：Objective To investigate the expression characteristics, clinical significance, and molecular mechanisms of transmembrane protein 147(TMEM147) in regulating hepatocellular carcinoma(HCC) progression. Methods The cancer genome atlas(TCGA) database, immunohistochemistry(IHC), quantitative real-time PCR(qRT-PCR), and Western blot(WB) were utilized to analyze TMEM147 expression and prognostic value in HCC. Small interfering RNA and overexpression plasmids were employed to modulate TMEM147 expression, while CCK-8, EdU, Transwell, wound healing assays, and nude mouse subcutaneous xenograft models were used to evaluate its effects on HCC cell proliferation and metastasis. Transcriptome sequencing(RNA-seq) and PI3K/AKT pathway inhibitor(LY294002) were applied to explore the molecular mechanisms underlying TMEM147-driven HCC progression. Results TCGA data, IHC, qRT-PCR, and WB revealed that TMEM147 was significantly upregulated in HCC(P<0.05), and high TMEM147 expression was correlated with shorter overall survival(P<0.001). Multivariate Cox regression analysis identified TMEM147 as an independent prognostic risk factor for HCC patients(P=0.01). Knockdown of TMEM147 inhibited HCC cell proliferation and migration(P<0.05), while overexpression of TMEM147 significantly enhanced these phenotypes(P<0.05). In vivo, TMEM147 overexpression led to increased tumor weight and volume(P<0.05) and elevated expression of proliferation markers Ki-67 and PCNA. RNA-seq analysis demonstrated that TMEM147 activated the PI3K/AKT signaling pathway to drive HCC progression, and PI3K inhibitor LY294002 reversed its pro-tumorigenic effects. Conclusion TMEM147 is highly expressed in HCC and associated with poor prognosis. It promotes tumor proliferation and metastasis via PI3K/AKT pathway activation, suggesting its potential as a prognostic biomarker and therapeutic target for HCC.
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基本信息:
DOI：10.19367/j.cnki.2096-8388.2026.01.001
中图分类号:R735.7
引用信息:
[1]王智,张业伟,左石.TMEM147通过PI3K/AKT信号通路促进肝癌细胞增殖转移的机制研究[J].贵州医科大学学报,2026,51(01):1-13.DOI:10.19367/j.cnki.2096-8388.2026.01.001.
基金信息:
国家自然科学基金项目(82260535)
2026-01-19
2026-01-19