title: Long noncoding RNA MALAT1 affects the efficacy of radiotherapy for esophageal squamous cell carcinoma by regulating Cks1 expression.
abstract: OBJECTIVE
  Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been well studied in the progression of many malignancies. However, its association with the radioresistance of tumors has not been well understood yet. This study tried to explore the role of MALAT1 in regulating the radiosensitivity of esophageal cancer (EC), especially esophageal squamous cell carcinoma (ESCC), involving its regulation on Cks1 expression.
  
  
  METHODS
  KYSE150 cells were subcutaneously inoculated into nude mice to establish ESCC xenografts. Real-time PCR and Western blot analysis were performed to detect the expression of MALAT1 and Cks1 in irradiated xenografts and cells. Functional analysis was performed in both EC9706 and KYSE150 cells via the transfection of corresponding plasmids or small interfering RNAs (siRNAs). Irradiation-induced damage was examined by the detection of cell viability and apoptosis using MTT and TUNEL assays, respectively.
  
  
  RESULTS
  Both MALAT1 and Cks1 were downregulated in irradiated xenografts and cells. Cks1FER1L4 showed significant downregulation. Overexpression of MALAT1 inhibited irradiation-induced decrease in cell viability, increase in apoptosis, and downregulation of Cks1. Cks1 expression was also downregulated by MALAT1 siRNA, while Cks1 siRNA strongly recovered MALAT1-induced radioresistance in vitro. Moreover, better tumor growth, accompanied by Cks1 upregulation, was observed in KYSE150 xenografts with MALAT1 overexpression, especially under radiation treatment.
  
  
  CONCLUSIONS
  MALAT1 acted as one positive regulator of the radioresistance of ESCC, at least partly due to its promotion on Cks1 expression. Furthermore, MALAT1-targeted therapies showed great potential in enhancing the radiotherapeutic effect on ESCC.
authors.affiliation: Department of Radiation Oncology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tu
authors.affiliation: Department of Radiation Oncology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bu
authors.affiliation: Department of Radiation Oncology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot, China.
authors.forename: Aqiu
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Kong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: C093090:CKS1B protein, human; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D042846:CDC2-CDC28 Kinases
keywords: Cks1; MALAT1; esophageal squamous cell carcinoma; radioresistance