Lung adenocarcinoma (LUAD) is a common type of lung cancer characterized by a high incidence of local invasion and metastasis. Programmed cell death factor 4 (PDCD4) is a well-recognized tumor suppressor gene involved in LUAD, however its precise regulatory mechanism remains elusive. This is the first study to report an inverse regulatory relationship between PDCD4 and eukaryotic translation initiation factor 3 subunit H (EIF3H) in LUAD. Co-immunoprecipitation assays combined with mass spectrometry and immunofluorescent co-localization indicated that PDCD4 interacted with EIF3H. Overexpression of PDCD4 in LUAD cells reduced EIF3H mRNA and protein levels by suppressing c-Jun-induced EIF3H transcription. Further, an elevated level of EIF3H protein was found in LUAD tissues compared with para-cancerous normal lung tissues, and was found to be an unfavorable factor promoting LUAD pathogenesis. Moreover, the negative correlation between PDCD4 and EIF3H protein expression was confirmed in LUAD tissues. Functional analyses showed that EIF3H overexpression promoted LUAD cell migration and invasion in vitro as well as metastasis in nude mice by activating epithelial-mesenchymal transition (EMT) signaling. Conversely, EIF3H knockdown with small interfering RNAs reversed these changes in LUAD cells. Furthermore, we discovered that introduction of PDCD4 to EIF3H-overexpressing LUAD cells abrogated the function of EIF3H, reducing migration and invasion of LUAD cells by downregulating EMT signaling. Taken together, our findings identified a previously unknown negative regulation of PDCD4 on EIF3H and confirmed EIF3H as an oncogenic factor in LUAD by enhancing EMT signaling, which was abrogated by PDCD4.
Keywords: EIF3H; Lung adenocarcinoma; PDCD4; invasion; metastasis.
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