MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma

Cheng Han Lin, Chen Hsun Tsai, Ching Tung Yeh, Jui Lin Liang, Wan Chun Hung, Forn Chia Lin, Wei Lun Chang, Hao Yi Li, Yun Chin Yao, Tai I. Hsu, Yu Cheng Lee, Yi Ching Wang, Bor Shyang Sheu, Wu Wei Lai, Marcus J. Calkins, Michael Hsiao, Pei Jung Lu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10-20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3'UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR- 193a-5p expression.

Original languageEnglish
Pages (from-to)39680-39693
Number of pages14
JournalOncotarget
Volume7
Issue number26
DOIs
Publication statusPublished - 2016 Jan 1

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Radiation Tolerance
Therapeutics
Esophageal Neoplasms
Animal Disease Models
Recurrence
Esophageal Squamous Cell Carcinoma
Receptor Protein-Tyrosine Kinases
3' Untranslated Regions
Carcinogenesis
Up-Regulation
Neoplasms
In Vitro Techniques
Trastuzumab

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Lin, Cheng Han ; Tsai, Chen Hsun ; Yeh, Ching Tung ; Liang, Jui Lin ; Hung, Wan Chun ; Lin, Forn Chia ; Chang, Wei Lun ; Li, Hao Yi ; Yao, Yun Chin ; Hsu, Tai I. ; Lee, Yu Cheng ; Wang, Yi Ching ; Sheu, Bor Shyang ; Lai, Wu Wei ; Calkins, Marcus J. ; Hsiao, Michael ; Lu, Pei Jung. / MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma. In: Oncotarget. 2016 ; Vol. 7, No. 26. pp. 39680-39693.
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title = "MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma",
abstract = "Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10-20{\%} of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3'UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR- 193a-5p expression.",
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Lin, CH, Tsai, CH, Yeh, CT, Liang, JL, Hung, WC, Lin, FC, Chang, WL, Li, HY, Yao, YC, Hsu, TI, Lee, YC, Wang, YC, Sheu, BS, Lai, WW, Calkins, MJ, Hsiao, M & Lu, PJ 2016, 'MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma', Oncotarget, vol. 7, no. 26, pp. 39680-39693. https://doi.org/10.18632/oncotarget.9444

MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma. / Lin, Cheng Han; Tsai, Chen Hsun; Yeh, Ching Tung; Liang, Jui Lin; Hung, Wan Chun; Lin, Forn Chia; Chang, Wei Lun; Li, Hao Yi; Yao, Yun Chin; Hsu, Tai I.; Lee, Yu Cheng; Wang, Yi Ching; Sheu, Bor Shyang; Lai, Wu Wei; Calkins, Marcus J.; Hsiao, Michael; Lu, Pei Jung.

In: Oncotarget, Vol. 7, No. 26, 01.01.2016, p. 39680-39693.

Research output: Contribution to journalArticle

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T1 - MiR-193a-5p/ERBB2 act as concurrent chemoradiation therapy response indicator of esophageal squamous cell carcinoma

AU - Lin, Cheng Han

AU - Tsai, Chen Hsun

AU - Yeh, Ching Tung

AU - Liang, Jui Lin

AU - Hung, Wan Chun

AU - Lin, Forn Chia

AU - Chang, Wei Lun

AU - Li, Hao Yi

AU - Yao, Yun Chin

AU - Hsu, Tai I.

AU - Lee, Yu Cheng

AU - Wang, Yi Ching

AU - Sheu, Bor Shyang

AU - Lai, Wu Wei

AU - Calkins, Marcus J.

AU - Hsiao, Michael

AU - Lu, Pei Jung

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10-20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3'UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR- 193a-5p expression.

AB - Concurrent chemoradiation therapy (CCRT) is the predominant treatment in esophageal cancer, however resistance to therapy and tumor recurrence are exceedingly common. Elevated ERBB2/Her2 may be at least partially responsible for both the high rates of recurrence and resistance to CCRT. This receptor tyrosine kinase is upregulated in 10-20% of esophageal squamous cell carcinoma (ESCC) tissues, and amplification of ERBB2 has been correlated with poor prognosis in esophageal cancer. Tissues from 131 ESCC patients, along with cell and animal models of the disease were used to probe the underlying mechanisms by which ERBB2 upregulation occurs and causes negative outcomes in ESCC. We found that overexpression of ERBB2 inhibited radiosensitivity in vitro. Furthermore, miR-193a-5p reduced ERBB2 expression by directly targeting the 3'UTR. Increased miR-193a-5p enhanced radiosensitivity and inhibited tumorigenesis in vitro and in vivo. Additionally, low miR-193a-5p expression correlated with poor prognosis in ESCC patients, and ESCC patients with good CCRT response exhibited higher miR-193a-5p expression. Our data suggest that patients with high miR-193a-5p will likely benefit from CCRT treatment alone, however a combination of CCRT with Herceptin may be beneficial for patients with low miR- 193a-5p expression.

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