Background: Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC). Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been reported to be involved in the progression, metastasis and recurrence of malignancies. However, the potential role of LPCAT1 in NSCLC remains poorly understood. This study was aimed to identify genes involved in lung adenocarcinoma (LUAD) brain metastasis, and look into the role of LPCAT1 in LUAD progression.
Methods: We used integrative genomic analysis to identify genes involved in lung adenocarcinomas. LPCAT1 expression was evaluated in tumor tissues from LUAD patients and LUAD cell lines. The role of LPCAT1 was subsequently investigated both in vitro and in vivo. The mechanism underlying the involvement of LPCAT1 in LUAD progression was explored with the activator of PI3K/AKT pathway. RNA sequencing was performed to confirm the involvement of LPCAT1 and associated pathway in LUAD brain metastasis.
Results: LPCAT1 was up-regulated in LUAD tissues and cell lines. shRNA-mediated depletion of LPCAT1 not only abrogated cell proliferation, migration and invasion in vitro, but also arrested tumor growth and brain metastases in vivo. Notably, LPCAT1 at least partially influenced LUAD progression through PI3K/AKT signal pathway by targeting MYC transcription. Moreover, expression of LPCAT1 was higher in tissues of LUAD patients with BM than those without BM as revealed by IHC staining, RNA-Sequencing and qPCR analysis. Finally, elevated LPCAT1 expression in patients with lung adenocarcinomas was associated with a poor clinical outcome.
Conclusions: This study showed that LPCAT1 works as a regulator of cell metastasis and may serve as a novel therapeutic target for BM in lung adenocarcinoma.
Keywords: Brain metastasis; LPCAT1; MYC; NSCLC; PI3K/AKT pathway; RNA-sequencing.