title: Let-7 expression is a significant determinant of response to chemotherapy through the regulation of IL-6/STAT3 pathway in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  Cisplatin-based chemotherapy is widely used for esophageal cancer, sometimes in combination with surgery/radiotherapy, but poor response to chemotherapy is not uncommon. The aim of this study was to examine whether miRNA expression is useful to predict the response to chemotherapy in patients with esophageal cancer.
  
  
  METHODS
  Using pretreatment biopsy samples from 98 patients with esophageal cancer who received preoperative chemotherapy, we measured the expression level of several miRNAs whose expression was altered in cisplatin-resistant esophageal cancer cell lines compared with those parent cell lines and examined the relationship between the miRNA expression and response to chemotherapy. In vitro assays were conducted to clarify the mechanism of miRNA-induced changes in chemosensitivity.
  
  
  RESULTS
  The expression levels of 15 miRNAs were altered in cisplatin-resistant cells. Of these, low expression of let-7b and let-7c in before-treatment biopsies from 74 patients of the training set correlated significantly with poor response to chemotherapy, both clinically and histopathologically. Low expression of let-7c also correlated with poor prognosis (P = 0.032). The relationship between let-7b and let-7c expression and response to chemotherapy was confirmed in the other 24 patients of the validation set. In in vitro assay, transfection of let-7c restored sensitivity to cisplatin and increased rate of apoptosis after exposure to cisplatin. Let-7c directly repressed cisplatin-activated interleukin (IL)-6/STAT3 prosurvival pathway.
  
  
  CONCLUSIONS
  Let-7 expression in esophageal cancer can be potentially used to predict the response to cisplatin-based chemotherapy. Let-7 modulates the chemosensitivity to cisplatin through the regulation of IL-6/STAT3 pathway in esophageal cancer.
authors: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamada oka, Suita, Osaka, Japan.
authors: Keijiro
authors: K
authors: Sugimura
authors: Hiroshi
authors: H
authors: Miyata
authors: Koji
authors: K
authors: Tanaka
authors: Rie
authors: R
authors: Hamano
authors: Tsuyoshi
authors: T
authors: Takahashi
authors: Yukinori
authors: Y
authors: Kurokawa
authors: Makoto
authors: M
authors: Yamasaki
authors: Kiyokazu
authors: K
authors: Nakajima
authors: Shuji
authors: S
authors: Takiguchi
authors: Masaki
authors: M
authors: Mori
authors: Yuichiro
authors: Y
authors: Doki
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D015850:Interleukin-6; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C487931:mirnlet7 microRNA, human