title: Inhibition of microRNA-21 increases radiosensitivity of esophageal cancer cells through phosphatase and tensin homolog deleted on chromosome 10 activation.
abstract: The radioresistance of esophageal squamous cell carcinoma is a great obstacle to treatment. Although it has been demonstrated that microRNA-21 (miR-21) can act as an 'oncogene' in esophageal squamous cell carcinoma, its role in radioresistance remains unexplored. The aims of this study were to investigate the role of miR-21 in esophageal squamous carcinoma cells' radioresistance and to identify the possible mechanism. The relatively radioresistant esophageal squamous cancer TE-1 cells (TE-R60) was established by fractionated irradiation. By lentiviral transduction with miRZip-21, the miR-21 expression in TE-1 cells was stably downregulated, which was renamed as 'anti-miR-21 TE-1 cells.' The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was knocked down in anti-miR-21 TE-1 cells through short interfering RNA. The expression level of miR-21 and PTEN messenger RNA were measured by quantitative real-time reverse transcription polymerase chain reaction or reverse transcription polymerase chain reaction. The expression level of PTEN, phospho-Akt, and Akt protein were detected by Western blot. Clongenic assay was used to analyze the cells' radiosensitivity. miR-21 was overexpressed, and PTEN was suppressed in established radioresistant TE-R60 cells compared with the parent cells (1.3-fold and 70.83%). The inhibition of miR-21 significantly increased the cells' radiosensitivity (P < 0.05) and the PTEN protein expression (2.3-fold) in TE-1 cells. In addition, phospho-Akt protein, downstream target of PTEN, reduced significantly in anti-miR-21 TE-1 cells. Knockdown of PTEN in anti-miR-21 TE-1 cells could abrogate the miR-21 inhibition-induced radiosensitization (P < 0.05). Inhibition of miR-21 increased radiosensitivity of esophageal cancer TE-1 cells, and this effect was possibly through the activation of PTEN. Inhibition of miR-21 may form a novel therapeutic strategy to increase the radiosensitivity of esophageal cancer.
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China Center for Molecular Medicine, First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China.
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: S-M
authors.initials: SM
authors.lastname: Che
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: X-Z
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014410:Tumor Stem Cell Assay
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human