Migration and Invasion Enhancer 1 Is an NF-ĸB-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo.

Chang Chang,Juang Juang,Feng Feng,Hou Hou,Lin Lin,Tsui Tsui

doi:10.3390/cancers11101486

Chang Chang, Juang Juang + Show 4 more

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https://doi.org/10.3390/cancers11101486

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Journal: Cancers	Publication Date: Oct 2, 2019
Citations: 13	License type: CC BY 4.0

Affiliation: Chang Gung University, Chang Gung Memorial Hospital

Abstract

Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. We determined the expression, biological functions, and regulatory mechanisms of MIEN1 in the prostate. The results of immunohistochemical analysis indicated that MIEN1 was expressed specifically in epithelial cells and significantly higher in adenocarcinoma as compared to in normal tissues. MIEN1 enhanced in vitro cell proliferation, invasion, and in vivo tumorigenesis. Meanwhile, MIEN1 attenuated cisplatin-induced apoptosis in PC-3 cells. Overexpression of NF-ĸB-inducing kinase (NIK) enhanced MIEN1 expression, while overexpression of NF-ĸB inhibitor α (IĸBα) blocked MIEN1 expression in PC-3 cells. In prostate carcinoma cells, MIEN1 provoked Akt phosphorylation; moreover, MIEN1 downregulated N-myc downstream regulated 1 (NDRG1) but upregulated interleukin-6 (IL-6) gene expression. MK2206, an Akt inhibitor, impeded the modulation of MIEN1 on NDRG1 and IL-6 expressions. Our studies suggest that MIEN1 is an NF-ĸB downstream oncogene in the human prostate. Accordingly, the modulation of Akt signaling in the gene expressions of NDRG1 and IL-6 may account for the functions of MIEN1 in cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells.

Highlights

Migration and invasion enhancer 1 (MIEN1/C35/C17orf37), as an oncogenic gene, is located on chromosome 17q12 and 505 nucleotides from the 30 end of the ERBB2 oncogene [1,2]
The intense scores of MIEN1 immunostaining in normal prostate tissues were significantly lower than those in high-grade prostate cancer tissues, the results showed no significant differences between grade II and grade III
Our study revealed that MIEN1 expression among the prostate carcinoma cell lines was dependent on the cell type but not relevant to the extent of neoplasia in vitro, further immunohistochemical assay (IHC) analysis of a human prostate tissue array indicated that MIEN1 immunostaining in normal prostate tissues was less significant than that in high-grade prostate cancer tissues (Figure 1)

Summary

Introduction

Migration and invasion enhancer 1 (MIEN1/C35/C17orf37), as an oncogenic gene, is located on chromosome 17q12 and 505 nucleotides from the 30 end of the ERBB2 oncogene [1,2]. Cancers 2019, 11, 1486 suggesting that MIEN1 overexpression represents an oncogenic nature in the promotion of tumor cell dissemination and metastasis in breast cancer in vitro and in vivo [7,10]. The latest research stated that knockdown of the MIEN1 gene did not alter the morphology, development, proliferation, or survival of breast cancer cells [11]. A previous study disclosed that MIEN1 was expressed in the cytosol with intense staining in the membrane of prostate carcinoma cells, and it functionally enhanced migration and invasion via NF-κB/Akt activity [12]. It was found that a novel miRNA, has-miR-940 (miR-940), reduced the anchorage-independent development capacity and enhanced mesenchymal-to-epithelial transition via the blockage of MIEN1 expression by inhibiting the migratory and invasive potential of prostate carcinoma cells [13]. Further study indicated that hypomethylation of the SINE Alu region of the MIEN1 promoter and upstream stimulatory factor 1 (USF1) binding triggered MIEN1 expression in prostate cancer in vitro and in vivo [6]

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