Monoacylglycerol Lipase Knockdown Inhibits Cell Proliferation and Metastasis in Lung Adenocarcinoma

基因敲除 癌症研究 生物 细胞周期蛋白D1 细胞生长 小发夹RNA 转移 腺癌 单酰甘油脂肪酶 细胞培养 癌症 细胞 细胞周期 生物化学 遗传学 受体 内大麻素系统
作者
Hao Zhang,Wei Guo,Fan Zhang,Renda Li,Yang Zhou,Fei Shao,Xiaoli Feng,Fengwei Tan,Jie Wang,Shugeng Gao,Yibo Gao,Jie He
出处
期刊:Frontiers in Oncology [Frontiers Media]
卷期号:10: 559568-559568 被引量:23
标识
DOI:10.3389/fonc.2020.559568
摘要

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.
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