〔Abstract〕 ObjectiveTo investigate the effects of 7-dehydrocholesterol reductase (DHCR7) in promoting proliferation, migration, and invasion of lung adenocarcinoma cells and the underlying signaling mechanisms. Methods The expression level of DHCR7 in lung adenocarcinoma and its prognosis were analyzed by using public databases. DHCR7 protein expression levels in the lung adenocarcinoma cell lines H1299 and A549 were assessed by Western blot, using the normal lung epithelial cell line BEAS-2B as a control. Small interfering RNA (siRNA) was used to knock down DHCR7 expression in H1299 and A549 cells. Assays including colony formation, CCK-8, wound healing, and Transwell experiments were conducted to assess the proliferation, migration, and invasion of the knockdown cells. Next, Western blot was employed to assess the phosphorylation levels of key signaling molecules in the Phosphoinositide 3-kinase/Protein Kinase B (PI3K/AKT), Janus Kinase/Signal Transducer and Activator of Transcription 3 (JAK/STAT3),Mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) (p-AKT, p-STAT3, p-ERK). ResultsBioinformatics results indicated that both DHCR7 mRNA and protein were highly expressed in lung adenocarcinoma compared with normal tissues adjacent to cancer. Furthermore, higher DHCR7 mRNA level was associated with poor prognosis ( P< 0.001). The expression levels of DHCR7 were significantly higher in both H1299 and A549 cells than that in BEAS-2B cells ( P< 0.05, P< 0.01). Compared with si-Control, the proliferation, migration, and invasion abilities of si- DHCR7 H1299 and A549 cells significantly decreased. Among the phosphorylated signaling molecules detected, p-ERK was significantly downregulated ( P< 0.000 1, P< 0.01) whereas p-AKT and p-STAT3 levels were not significantly changed. ConclusionDHCR7 has prominent effects in promoting the proliferation, migration, and invasion of lung adenocarcinoma cells, and the underlying mechanisms are related to the MAPK/ERK signaling pathway.