Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism

Jieun Lee, Sung Ho Goh, Naaleum Song, Jung Ah Hwang, Seungyoon Nam, Il Ju Choi, Aesun Shin, In Hoo Kim, Mi Ha Ju, Jin Sook Jeong, Yeon Su Lee

Research output: Contribution to journalArticle

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Abstract

In an effort to identify novel genes related to the prognosis of gastric cancer, we performed gene expression profiling and found overexpressed levels of human interferon-induced transmembrane protein 1 (IFITM1). We validated the gastric cancer-specific up-regulation of IFITM1 and its association with cancer progression. We also studied its epigenetic regulation and tumorigenesis-related functions. Expression of IFITM1 was evaluated in various human gastric cancer cells and in 35 patient tumor tissues by quantitative RT-PCR and Western blot analyses. The results showed highly up-regulated IFITM1 in cancer cell lines and tissues. Furthermore, IHC studies were performed on 151 patient tissues, and a significant correlation was revealed between higher IFITM1 expression and Lauren's intestinal type (P = 0.007) and differentiated adenocarcinoma (P = 0.025). Quantitative studies of DNA methylation for 27 CpG sites in the regulatory region showed hypermethylation in cells expressing low levels of IFITM1. Methylation-dependent IFITM1 expression was confirmed further by in vitro demethylation using 5-aza-2′-deoxycytidine and luciferase assays. The functional analysis of IFITM1 by silencing of its expression with small-interfering RNA showed decreased migration and invasiveness of cancer cells, whereas its overexpression exhibited the opposite results. In this study, we demonstrated gastric cancer-specific overexpression of IFITM1 regulated by promoter methylation and the role of IFITM1 in cancer prognosis.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalAmerican Journal of Pathology
Volume181
Issue number1
DOIs
StatePublished - 1 Jul 2012

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Epigenomics
Stomach Neoplasms
decitabine
Neoplasms
Methylation
leu-13 antigen
Nucleic Acid Regulatory Sequences
Neoplasm Genes
Gene Expression Profiling
DNA Methylation
Luciferases
Small Interfering RNA
Carcinogenesis
Adenocarcinoma
Up-Regulation
Western Blotting
Cell Line
Polymerase Chain Reaction

Cite this

Lee, Jieun ; Goh, Sung Ho ; Song, Naaleum ; Hwang, Jung Ah ; Nam, Seungyoon ; Choi, Il Ju ; Shin, Aesun ; Kim, In Hoo ; Ju, Mi Ha ; Jeong, Jin Sook ; Lee, Yeon Su. / Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism. In: American Journal of Pathology. 2012 ; Vol. 181, No. 1. pp. 43-52.
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title = "Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism",
abstract = "In an effort to identify novel genes related to the prognosis of gastric cancer, we performed gene expression profiling and found overexpressed levels of human interferon-induced transmembrane protein 1 (IFITM1). We validated the gastric cancer-specific up-regulation of IFITM1 and its association with cancer progression. We also studied its epigenetic regulation and tumorigenesis-related functions. Expression of IFITM1 was evaluated in various human gastric cancer cells and in 35 patient tumor tissues by quantitative RT-PCR and Western blot analyses. The results showed highly up-regulated IFITM1 in cancer cell lines and tissues. Furthermore, IHC studies were performed on 151 patient tissues, and a significant correlation was revealed between higher IFITM1 expression and Lauren's intestinal type (P = 0.007) and differentiated adenocarcinoma (P = 0.025). Quantitative studies of DNA methylation for 27 CpG sites in the regulatory region showed hypermethylation in cells expressing low levels of IFITM1. Methylation-dependent IFITM1 expression was confirmed further by in vitro demethylation using 5-aza-2′-deoxycytidine and luciferase assays. The functional analysis of IFITM1 by silencing of its expression with small-interfering RNA showed decreased migration and invasiveness of cancer cells, whereas its overexpression exhibited the opposite results. In this study, we demonstrated gastric cancer-specific overexpression of IFITM1 regulated by promoter methylation and the role of IFITM1 in cancer prognosis.",
author = "Jieun Lee and Goh, {Sung Ho} and Naaleum Song and Hwang, {Jung Ah} and Seungyoon Nam and Choi, {Il Ju} and Aesun Shin and Kim, {In Hoo} and Ju, {Mi Ha} and Jeong, {Jin Sook} and Lee, {Yeon Su}",
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Lee, J, Goh, SH, Song, N, Hwang, JA, Nam, S, Choi, IJ, Shin, A, Kim, IH, Ju, MH, Jeong, JS & Lee, YS 2012, 'Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism', American Journal of Pathology, vol. 181, no. 1, pp. 43-52. https://doi.org/10.1016/j.ajpath.2012.03.027

Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism. / Lee, Jieun; Goh, Sung Ho; Song, Naaleum; Hwang, Jung Ah; Nam, Seungyoon; Choi, Il Ju; Shin, Aesun; Kim, In Hoo; Ju, Mi Ha; Jeong, Jin Sook; Lee, Yeon Su.

In: American Journal of Pathology, Vol. 181, No. 1, 01.07.2012, p. 43-52.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism

AU - Lee, Jieun

AU - Goh, Sung Ho

AU - Song, Naaleum

AU - Hwang, Jung Ah

AU - Nam, Seungyoon

AU - Choi, Il Ju

AU - Shin, Aesun

AU - Kim, In Hoo

AU - Ju, Mi Ha

AU - Jeong, Jin Sook

AU - Lee, Yeon Su

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Y1 - 2012/7/1

N2 - In an effort to identify novel genes related to the prognosis of gastric cancer, we performed gene expression profiling and found overexpressed levels of human interferon-induced transmembrane protein 1 (IFITM1). We validated the gastric cancer-specific up-regulation of IFITM1 and its association with cancer progression. We also studied its epigenetic regulation and tumorigenesis-related functions. Expression of IFITM1 was evaluated in various human gastric cancer cells and in 35 patient tumor tissues by quantitative RT-PCR and Western blot analyses. The results showed highly up-regulated IFITM1 in cancer cell lines and tissues. Furthermore, IHC studies were performed on 151 patient tissues, and a significant correlation was revealed between higher IFITM1 expression and Lauren's intestinal type (P = 0.007) and differentiated adenocarcinoma (P = 0.025). Quantitative studies of DNA methylation for 27 CpG sites in the regulatory region showed hypermethylation in cells expressing low levels of IFITM1. Methylation-dependent IFITM1 expression was confirmed further by in vitro demethylation using 5-aza-2′-deoxycytidine and luciferase assays. The functional analysis of IFITM1 by silencing of its expression with small-interfering RNA showed decreased migration and invasiveness of cancer cells, whereas its overexpression exhibited the opposite results. In this study, we demonstrated gastric cancer-specific overexpression of IFITM1 regulated by promoter methylation and the role of IFITM1 in cancer prognosis.

AB - In an effort to identify novel genes related to the prognosis of gastric cancer, we performed gene expression profiling and found overexpressed levels of human interferon-induced transmembrane protein 1 (IFITM1). We validated the gastric cancer-specific up-regulation of IFITM1 and its association with cancer progression. We also studied its epigenetic regulation and tumorigenesis-related functions. Expression of IFITM1 was evaluated in various human gastric cancer cells and in 35 patient tumor tissues by quantitative RT-PCR and Western blot analyses. The results showed highly up-regulated IFITM1 in cancer cell lines and tissues. Furthermore, IHC studies were performed on 151 patient tissues, and a significant correlation was revealed between higher IFITM1 expression and Lauren's intestinal type (P = 0.007) and differentiated adenocarcinoma (P = 0.025). Quantitative studies of DNA methylation for 27 CpG sites in the regulatory region showed hypermethylation in cells expressing low levels of IFITM1. Methylation-dependent IFITM1 expression was confirmed further by in vitro demethylation using 5-aza-2′-deoxycytidine and luciferase assays. The functional analysis of IFITM1 by silencing of its expression with small-interfering RNA showed decreased migration and invasiveness of cancer cells, whereas its overexpression exhibited the opposite results. In this study, we demonstrated gastric cancer-specific overexpression of IFITM1 regulated by promoter methylation and the role of IFITM1 in cancer prognosis.

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