Abstract
Abnormal metabolism is one of the hallmarks of cancer cells. Monoacylglycerol lipase (MGLL), a key enzyme in lipid metabolism, has emerged as an important regulator of tumor progression. In this study, we aimed to characterize the role of MGLL in the development of lung adenocarcinoma (LUAD). To this end, we used tissue microarrays to evaluate the expression of MGLL in LUAD tissue and assessed whether the levels of this protein are correlated with clinicopathological characteristics of LUAD. We found that the expression of MGLL is higher in LUAD samples than that in adjacent non-tumor tissues. In addition, elevated MGLL expression was found to be associated with advanced tumor progression and poor prognosis in LUAD patients. Functional studies further demonstrated that stable short hairpin RNA (shRNA)-mediated knockdown of MGLL inhibits tumor proliferation and metastasis, both in vitro and in vivo, and mechanistically, our data indicate that MGLL regulates Cyclin D1 and Cyclin B1 in LUAD cells. Moreover, we found that knockdown of MGLL suppresses the expression of matrix metalloproteinase 14 (MMP14) in A549 and H322 cells, and in clinical samples, expression of MMP14 is significantly correlated with MGLL expression. Taken together, our results indicate that MGLL plays an oncogenic role in LUAD progression and metastasis and may serve as a potential biomarker for disease prognosis and as a target for the development of personalized therapies.
Highlights
Non-small cell lung cancer is one of the leading causes of cancer-related deaths worldwide, with lung adenocarcinoma (LUAD) representing the major subtype of this disease [1, 2]
It has become well recognized that aberrant expression of genes involved in fatty acid synthesis or fatty acid oxidation correlate with malignant phenotypes, including metastasis and drug resistance [22,23,24]
Monoacylglycerol lipase (MGLL) is an important enzyme in the process of lipolysis, and the oncogenic roles of MGLL have been validated in multiple tumors
Summary
Non-small cell lung cancer is one of the leading causes of cancer-related deaths worldwide, with lung adenocarcinoma (LUAD) representing the major subtype of this disease [1, 2]. Tumor progression and metastasis are recognized as main causes of death in patients with lung cancer [9, 10]. A number of studies have further demonstrated that aberrantly activated lipid metabolic pathways can promote cancer cell proliferation and metastasis [11,12,13], and intriguingly, disordered lipid metabolism has been detected in lung cancer [14].
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