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.
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.|Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Chen-Hsun
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Ching-Tung
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.|Department of General Surgery, Chi-Mei Medical Center, Liouying, Tainan 736, Taiwan.
authors.forename: Jui-Lin
authors.initials: JL
authors.lastname: Liang
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Hung
authors.affiliation: Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan 704, Taiwan.
authors.forename: Forn-Chia
authors.initials: FC
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.|Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan.
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Hao-Yi
authors.initials: HY
authors.lastname: Li
authors.affiliation: Clinical Medicine Research Center, National Cheng Kung University Hospital, Tainan 704, Taiwan.
authors.forename: Yun-Chin
authors.initials: YC
authors.lastname: Yao
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Tai-I
authors.initials: TI
authors.lastname: Hsu
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.|Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan.
authors.forename: Bor-Shyang
authors.initials: BS
authors.lastname: Sheu
authors.affiliation: Department of Surgery Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan.
authors.forename: Wu-Wei
authors.initials: WW
authors.lastname: Lai
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Calkins
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors.forename: Pei-Jung
authors.initials: PJ
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D000068878:Trastuzumab / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C546818:MIRN193 microRNA, human; C508053:ERBB2 protein, human
keywords: CCRT; ERBB2; esophageal squamous cell carcinoma; indicator; miR-193a-5p