Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells

Jin Sil Chung, Sunhoo Park, Seon Ho Park, Eun Ran Park, Pu Hyeon Cha, Bu Yeo Kim, Young Min Chung, Seon Rang Woo, Chul Ju Han, Sang Bum Kim, Kyung Suk Suh, Ja June Jang, Kyoungbun Lee, Dong Wook Choi, Sora Lee, Gi Young Lee, Ki Baik Hahm, Jung Ar Shin, Byung Soo Kim, Kyung Hee Noh & 3 others Tae Woo Kim, Kee Ho Lee, Young Do Yoo

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

BACKGROUND & AIMS: Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness. METHODS: We performed real-time, semi-quantitative, reverse transcriptase polymerase chain reaction; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95). RESULTS: Expression of Romo1 was increased in HCC cells, compared with normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased compared with normal liver tissues in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels of Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size. CONCLUSIONS: Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate up-regulated intracellular ROS, might be developed as cancer therapies.

Original languageEnglish
JournalGastroenterology
Volume143
Issue number4
DOIs
Publication statusPublished - 2012 Oct 1

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Hepatocytes
Hepatocellular Carcinoma
Reactive Oxygen Species
Neoplasms
Lung
SCID Mice
Tetradecanoylphorbol Acetate
Luciferases
Reverse Transcriptase Polymerase Chain Reaction
Fluorescent Antibody Technique
Blood Vessels
Mitochondria
Oxidative Stress
Fibroblasts
Biomarkers
Cell Line
Injections
Survival
Liver

Keywords

  • Chemotherapy Resistance
  • Liver Cancer
  • Metastasis
  • Prognostic Factor

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells. / Chung, Jin Sil; Park, Sunhoo; Park, Seon Ho; Park, Eun Ran; Cha, Pu Hyeon; Kim, Bu Yeo; Chung, Young Min; Woo, Seon Rang; Han, Chul Ju; Kim, Sang Bum; Suh, Kyung Suk; Jang, Ja June; Lee, Kyoungbun; Choi, Dong Wook; Lee, Sora; Lee, Gi Young; Hahm, Ki Baik; Shin, Jung Ar; Kim, Byung Soo; Noh, Kyung Hee; Kim, Tae Woo; Lee, Kee Ho; Yoo, Young Do.

In: Gastroenterology, Vol. 143, No. 4, 01.10.2012.

Research output: Contribution to journalArticle

Chung, JS, Park, S, Park, SH, Park, ER, Cha, PH, Kim, BY, Chung, YM, Woo, SR, Han, CJ, Kim, SB, Suh, KS, Jang, JJ, Lee, K, Choi, DW, Lee, S, Lee, GY, Hahm, KB, Shin, JA, Kim, BS, Noh, KH, Kim, TW, Lee, KH & Yoo, YD 2012, 'Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells', Gastroenterology, vol. 143, no. 4. https://doi.org/10.1053/j.gastro.2012.06.038
Chung, Jin Sil ; Park, Sunhoo ; Park, Seon Ho ; Park, Eun Ran ; Cha, Pu Hyeon ; Kim, Bu Yeo ; Chung, Young Min ; Woo, Seon Rang ; Han, Chul Ju ; Kim, Sang Bum ; Suh, Kyung Suk ; Jang, Ja June ; Lee, Kyoungbun ; Choi, Dong Wook ; Lee, Sora ; Lee, Gi Young ; Hahm, Ki Baik ; Shin, Jung Ar ; Kim, Byung Soo ; Noh, Kyung Hee ; Kim, Tae Woo ; Lee, Kee Ho ; Yoo, Young Do. / Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells. In: Gastroenterology. 2012 ; Vol. 143, No. 4.
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abstract = "BACKGROUND & AIMS: Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness. METHODS: We performed real-time, semi-quantitative, reverse transcriptase polymerase chain reaction; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95). RESULTS: Expression of Romo1 was increased in HCC cells, compared with normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased compared with normal liver tissues in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels of Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size. CONCLUSIONS: Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate up-regulated intracellular ROS, might be developed as cancer therapies.",
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T1 - Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells

AU - Chung, Jin Sil

AU - Park, Sunhoo

AU - Park, Seon Ho

AU - Park, Eun Ran

AU - Cha, Pu Hyeon

AU - Kim, Bu Yeo

AU - Chung, Young Min

AU - Woo, Seon Rang

AU - Han, Chul Ju

AU - Kim, Sang Bum

AU - Suh, Kyung Suk

AU - Jang, Ja June

AU - Lee, Kyoungbun

AU - Choi, Dong Wook

AU - Lee, Sora

AU - Lee, Gi Young

AU - Hahm, Ki Baik

AU - Shin, Jung Ar

AU - Kim, Byung Soo

AU - Noh, Kyung Hee

AU - Kim, Tae Woo

AU - Lee, Kee Ho

AU - Yoo, Young Do

PY - 2012/10/1

Y1 - 2012/10/1

N2 - BACKGROUND & AIMS: Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness. METHODS: We performed real-time, semi-quantitative, reverse transcriptase polymerase chain reaction; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95). RESULTS: Expression of Romo1 was increased in HCC cells, compared with normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased compared with normal liver tissues in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels of Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size. CONCLUSIONS: Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate up-regulated intracellular ROS, might be developed as cancer therapies.

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KW - Chemotherapy Resistance

KW - Liver Cancer

KW - Metastasis

KW - Prognostic Factor

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