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跨膜蛋白44作为肝细胞癌一种新的预后标志物,与肿瘤侵袭、迁移及凋亡相关。

TMEM44 as a Novel Prognostic Marker for Hepatocellular Carcinoma is Associated with Tumor Invasion, Migration, and Apoptosis.

作者信息

Wu Zhipeng, Qiu Bingbing, Liu Shuiqiu, Hong Yiran, Sun Liang, Yin Xiangbao, Huang Yonge, Chen Zhendong

机构信息

Department of Hepatobiliary Surgery, Jiangxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Nanchang, China.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

出版信息

Biochem Genet. 2025 Jun 20. doi: 10.1007/s10528-025-11161-9.

Abstract

The transmembrane protein (TMEM) family represents a class of integral membrane proteins that traverse the lipid bilayer and play pivotal roles in diverse cellular processes. Functioning as molecular channels or regulators, TMEM proteins mediate selective transmembrane transport and have been implicated in the pathogenesis and progression of multiple malignancies. However, the biological significance of TMEM44 in hepatocellular carcinoma (HCC) remains largely unexplored. Through integrated bioinformatics analysis of clinical datasets, we identified significant upregulation of TMEM44 in HCC tissues, which correlated with adverse prognostic indicators. This overexpression was further validated at both protein and transcriptional levels via Western blotting and quantitative reverse transcription PCR (RT-qPCR) in HCC-derived cell lines and patient specimens. Functional characterization employing loss-of-function approaches in HCCLM3 and Huh-7 cell models demonstrated that TMEM44 silencing markedly attenuated malignant phenotypes: Transwell migration assays and wound healing analysis revealed impaired cellular motility, while 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays showed suppressed proliferation. Furthermore, flow cytometric analysis indicated induced cell cycle arrest at the G0/G1 phase and enhanced apoptotic susceptibility upon TMEM44 knockdown. Collectively, our results identify TMEM44 as a critical oncogenic regulator in HCC, underscoring its dual potential as a prognostic biomarker and a therapeutic target for precision oncology.

摘要

跨膜蛋白(TMEM)家族是一类整合膜蛋白,它们贯穿脂质双层,在多种细胞过程中发挥关键作用。作为分子通道或调节因子,TMEM蛋白介导选择性跨膜运输,并与多种恶性肿瘤的发病机制和进展有关。然而,TMEM44在肝细胞癌(HCC)中的生物学意义在很大程度上仍未被探索。通过对临床数据集进行综合生物信息学分析,我们发现HCC组织中TMEM44显著上调,这与不良预后指标相关。通过蛋白质印迹法和定量逆转录PCR(RT-qPCR)在HCC衍生的细胞系和患者标本中,在蛋白质和转录水平上进一步验证了这种过表达。在HCCLM3和Huh-7细胞模型中采用功能丧失方法进行功能表征表明,TMEM44沉默显著减弱了恶性表型:Transwell迁移试验和伤口愈合分析显示细胞运动性受损,而5-乙炔基-2'-脱氧尿苷(EdU)掺入试验显示增殖受到抑制。此外,流式细胞术分析表明,TMEM44敲低后诱导细胞周期停滞在G0/G1期,并增强了细胞凋亡敏感性。总之,我们的结果确定TMEM44是HCC中的关键致癌调节因子,强调了其作为预后生物标志物和精准肿瘤学治疗靶点的双重潜力。

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