NudCD1 Promotes the Proliferation and Metastasis of Non-Small Cell Lung Cancer Cells through the Activation of IGF1R-ERK1/2

Abstract

Background: NudC domain containing 1 (NudCD1) is an oncoprotein related to diverse cancers. This study aims to investigate the expression, role, and regulatory mechanism of NudCD1 in non-small cell lung cancer (NSCLC). Methods: qRT-PCR, Western blot, and immunohistochemistry were performed to detect the expressions of NudCD1 in NSCLC tissues and cell lines. The correlation between NudCD1 expression and clinical features was determined by the χ 2 test. Besides, shRNA was used to construct the NudCD1 low expression model of NCI-H1299 and NCI-H460 cells, and CCK-8 and transwell assay were conducted to monitor the changes of proliferation, migration, and invasion of cancer cells. The expression levels of epithelial-mesenchymal transition markers and IGF1R-ERK1/2 signaling pathway proteins were detected by Western blot. Results: The expression of NudCD1 in NSCLC was higher than that in normal tissues, and the increased expression of NudCD1 was significantly correlated with increased T stage and lymph node metastasis. Moreover, patients with high expression of NudCD1 had worse prognosis. NudCD1 knockdown was proven to impede the proliferation but facilitate the migration and invasion of cancer cells. Furthermore, knockdown of NudCD1 resulted in an increase in the expression of E-cadherin and a decrease in the expression of vimentin. We also observed that NudCD1 overexpression promoted the phosphorylation of IGF1R and ERK1/2 proteins. Conclusion: NudCD1 promotes the proliferation and metastasis of NSCLC cells via activation of IGF1R-ERK1/2, which indicates that NudCD1 may be a potential therapy target of NSCLC.

Quantifying the contribution of transcription factor activity, mutations and microRNAs to CD274 expression in cancer patients

“…For instance, LUAD tumors with high PD-L1 expression levels are frequently mutated in NUDCD1, which is involved in cell proliferation, migration, and invasion 53 . It exerts oncogenic functions via regulating the IGF1R-ERK pathway in NSCLC cells 54 . IGF1R activation mediates the activation of PI3K signaling, which regulates PD-L1 expression by either transcriptional or post-transcriptional mechanisms 55 , 56 .…”

LncRNA Opa interacting protein 5‐antisense RNA 1 (OIP5‐AS1) promotes the migration, invasion and epithelial‐mesenchymal transition (EMT) through targeting miR‐147a/insulin‐like growth factor 1 receptor (IGF1R) pathway in cervical cancer tissues and cell model

“…IGF1R is an important tumor-promoting growth factor, which has the effects of promoting cell mitosis, metastasis, and inhibiting apoptosis. 22 IGF1R has the ability to inhibit apoptosis and promote cell proliferation and survival, and has been identified as a potential therapeutic target for patients with a variety of different malignancies. 5 For example, has_circ_002577 accelerated endometrial cancer by up-regulating IGF1R.…”

Construction of a MicroRNA-mRNA Network Underlying Decidualized Endometriotic Cyst Stromal Cells Using Bioinformatics Analysis

“…Among the 14 overlapping genes, we found 6 downregulated mRNAs and 8 upregulated mRNAs in decidualized ECSCs. Some of them have been reported to play important roles in the development of tumor proliferation, apoptosis, and metastasis, such as IGF1R [ 21 ], MYBL2 [ 22 ], POLE [ 23 ], and DDAH1 [ 24 ]. Some of them were involved in various inflammatory and immune responses, such as PDE4D [ 25 ] and IRF2BP2 [ 26 ].…”