title: The Plasma microRNA miR-1914* and -1915 Suppresses Chemoresistant in Colorectal Cancer Patients by Down-regulating NFIX.
abstract: OBJECTIVE
  We investigated mechanisms of colorectal cancer (CRC) chemoresistance to first-line chemotherapy (capecitabine plus oxaliplatin (XELOX)) and identified two putative chemoresistant microRNAs, miR-1914* and -1915, that are downregulated in plasma samples from patients with chemoresistant CRC.
  
  
  METHODS
  A number of plasma samples from CRC patients were analyzed for the levels of miR-1914* and - 1915. Effects of stable and transient expression of 2 microRNAs in human chemoresistant CRC cell lines were analyzed. Tumor formation and chemoresistance in HCT116/5-Fu/OXA that did or did not express 2 microRNAs were analyzed in mice. Nuclear factor I/X (NFIX) was predicted to target the gene of 2 miRNAs and verified in vivo and in vitro.
  
  
  RESULTS
  Plasma levels of miR-1914* and -1915 in chemoresistant CRC patients were different than levels in responders, and associated with clinical response. Overexpression of miR-1914* and -1915 in chemoresistant CRC cells reduced resistance to 5-FU and Oxaliplatin in vitro. The microRNAs suppressed chemoresistance in CRC tumors in mice by affecting cell growth, invasion, apoptosis and tumor suppressor function. miR-1914* and -1915 interacted with the 3'-untranslated region of NFIX and reduced NFIX its level in chemoresistant CRC cells. Overexpression of NFIX did not inhibit chemoresistant CRC cell motility and chemoresistant proteins when miR-1914* and -1915 were transfected.
  
  
  CONCLUSIONS
  Plasma miR-1914* and -1915 interact with NFIX RNA and reduce its level in chemoresistant CRC cells to first-line chemotherapy. Up-regulation of miR-1914* and -1915 decreased the chemoresistance abilities of chemoresistant CRC cells. The plasma miR-1914* and -1915 may play a role in colorectal cancer therapy and diagnosis.
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: G
authors.initials: G
authors.lastname: Cai
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. hjs001@163.com.
authors.forename: S
authors.initials: S
authors.lastname: Cai
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000069287:Capecitabine / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D051839:NFI Transcription Factors / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D010071:Oxaloacetates
chemical_list: C578402:MIRN1915 microRNA, human; D035683:MicroRNAs; D051839:NFI Transcription Factors; C000594474:NFIX protein, human; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil