Origin recognition complex 1 regulates phospholipase Cδ1 to inhibit cell proliferation, migration and epithelial‑mesenchymal transition in lung adenocarcinoma

Abstract

As a common pulmonary malignant disease, lung adenocarcinoma exhibits high mortality and morbidity rate. Phospholipase Cδ1 (PLCD1), an enzyme involved in the homeostasis of energy metabolism, is downregulated in lung adenocarcinoma. According to GEPIA, origin recognition complex 1 (ORC1) is a highly expressed gene in lung adenocarcinoma and is negatively associated with PLCD1. To the best of our knowledge, the present study was the first to investigate the role of ORC1 in regulating PLCD1 in lung adenocarcinoma. According to TCGA database, low expression of PLCD1 was correlated with the low overall survival rate of patients suffering from lung adenocarcinoma. The protein and mRNA expression levels of PLCD1 and ORC1 were detected in A549 cells by western blot analysis and reverse transcription-quantitative PCR, respectively. Cell proliferation, invasion and migration were analyzed by MTT, colony formation, Transwell and wound healing assay. Immunofluorescence staining was adopted to estimate the content of Ki67 and western blot was applied for the evaluation of PLCD1, MMP2, MMP9, E-cadherin, N-cadherin, vimentin, Snail and ORC. The binding interaction between ORC1 and PLCD1 was analyzed using chromatin immunoprecipitation and luciferase reporter enzyme gene assays. The results indicated that PLCD1 was lowly expressed in lung adenocarcinoma cells in comparison with that in 16HBE. When PLCD1 was overexpressed in cancer cells, cell proliferation, invasion and migration were significantly inhibited. However, in the presence of both ORC1 and PLCD1 overexpression, the suppressive effects of PLCD1 overexpression alone on cell proliferation, invasion, migration and EMT were attenuated. In conclusion, ORC1 was indicated to inhibit PLCD1, thus regulating the proliferation, migration and EMT processes of lung adenocarcinoma cells, which suggested that ORC1 might be a target for the treatment of lung adenocarcinoma.

Stemness genes and miR-1247-3p expression associate with clinicopathological parameters and prognosis in lung adenocarcinoma

“…Recently, aberrations in ORC1L have been implicated in breast cancer [66], cervical cancer [67], as well as LUAD cancer progression [68]. Investigating the role of ORC1L more closely, we found that aberrations in ORC1L gene expression have been previously linked with LUAD tumor growth [68,69] through changes in immune cell infiltration [68]. Han et al, [68] postulated that ORC1L promotes LUAD tumor progression and aberration of immune infiltration by deregulating WNT signaling pathway.…”

Pick-up single-cell proteomic analysis for quantifying up to 3000 proteins in a Mammalian cell

“…8 , Wilcoxon test, p.adj < 0.05, fold change > 2). Among them, the upregulated proteins such as Orc1 49 , TGFBI 50 , MSLN 51 , HtrA1 52 , 53 were reported to be associated with the migration and invasion of tumor cells. The expression levels of these proteins in the different clusters were quantified (Supplementary Fig.…”

Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches

“…In A549 cells, PLCδ1 overexpression inhibits proliferation, cell invasion, migration, and epithelial–mesenchymal transition in LC cells. Moreover, in A549 cells, ORC1 binds to the PLCδ1 promoter, significantly reducing PLCδ1 expression, which may affect the progression of LC [ 60 ]. PLCδ1 acts as a tumor-suppressor gene in various tumors, and it is epigenetically silenced through hypermethylation in esophageal squamous cell carcinoma, breast cancer, gastric cancer, and chronic myeloid leukemia [ 32 ].…”