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

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.