Abstract
BackgroundBrain 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.MethodsWe 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.ResultsLPCAT1 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.ConclusionsThis study showed that LPCAT1 works as a regulator of cell metastasis and may serve as a novel therapeutic target for BM in lung adenocarcinoma.
Highlights
Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC)
By searching tumor-related online databases and examining the gene expression in primary loci and adjacent tissues in healthy subjects and lung-cancer patients, we found that Lysophosphatidylcholine acyltransferase 1 (LPCAT1) was highly expressed in pulmonary tissues and its over-expression was correlated with the poor prognosis of NSCLC
Our results indicated that LPCAT1 was highly expressed in lung tumor tissues, and the LPCAT1 expression was even higher in lung tissues from lung cancer patients with brain metastasis
Summary
Brain metastasis (BM) is associated with poor prognosis, recurrence, and death in patients with non-small cell lung cancer (NSCLC). This study was aimed to identify genes involved in lung adenocarcinoma (LUAD) brain metastasis, and look into the role of LPCAT1 in LUAD progression. Brain metastasis (BM) is the main cause of poor prognosis, recurrence and death in NSCLC patients, and approximately 20–40% of these patients eventually developed BM [1]. Multiple studies showed that the PI3K/AKT was involved in brain metastases of breast cancer [6, 7] and melanoma [5, 6]. Inhibition of PI3K/AKT pathway might block brain metastasis of melanoma [6]. The function of PI3K/AKT pathway and MYC in brain metastases of NSCLC remains poorly understood
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