<p>MiR-203 acts as a radiosensitizer of gastric cancer cells by directly targeting ZEB1</p>
Authors: Qi Shen
Ying Jiang
Yingbo Xue
Shisheng Tan
Shan Jin
Journal: OncoTargets and Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: ZEB1; gastric cancer; miR-203; radiosensitivity; radiosensitizer.
Affiliations: Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, People's Republic of China.

Abstract:  Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Radiotherapy is one of the main strategies for GC treatment, while development of radioresistance limits the effectiveness. microRNA-203 (miR-203) has been reported to participate in progression of GC, whereas its interaction with radiosensitivity of GC and the related mechanism remain largely unclear. Methods: The expressions of miR-203 and zinc finger E-box binding homeobox 1 (ZEB1) were measured in GC tissues and cells by quantitative real-time polymerase chain reaction or western blot. Survival fraction, cell viability and apoptosis were measured in GC cells after treatment of radiation by colony formation, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay or flow cytometry, respectively. Tumor volume and weight were detected in murine xenograft model after radiation treatment. The interaction between miR-203 and ZEB1 was explored by bioinformatics analysis and luciferase activity assay. Results: miR-203 expression was down-regulated and ZEB1 mRNA level was up-regulated in GC. The expression of miR-203 was associated with radiosensitivity of GC cells. Moreover, overexpression of miR-203 decreased survival fraction, cell viability and tumor growth but promoted cell apoptosis in radiation-treated GC cells. However, knockdown of miR-203 played an opposite effect. ZEB1 was validated as a target of miR-203, and it was involved in miR-203-mediated radiosensitivity of GC cells in vitro and in vivo. Conclusion: miR-203 promoted radiosensitivity of GC cells by targeting ZEB1, indicating miR-203 as a promising radiosensitizer for GC treatment. 

Retracted: No

PubPeer comments:
 Figure 4D and figure 5B, figure 4E and figure 5A, respectively, look the same. However, from the two legends, they should be different. The authors seems to have accidentally reused a certain set of result images during the typesetting process. ![file] 4(D-G) The expression of ZEB1 was measured at protein and mRNA levels in MKN-45 cells transfected with miR-203 or miR-NC and AGS cells transfected with anti-miR-203 or anti-miR-NC by western blot or quantitative real-time polymerase chain reaction. 5(A and B) The expression of ZEB1 protein was measured in MKN-45 cells transfected with ZEB1 or vector and AGS transfected with shZEB1 or scrambled by western blot. , 
 *[left]* Fig 3D.  miR-203 promotes tumor inhibitory ability of radiation in mice. ... (C and D) The tumor volume and weight were detected in xenograft model formed by **AGS** stably transfected with anti-miR-203 or **anti-miR-NC** after treatment of radiation. *[right]* Fig 6D.  ZEB1 is involved in the regulatory role of miR-203 in radiation-treated mice. ... (C and D) The tumor volume and weight were detected in xenograft model formed by **AGS** stably transfected with anti-miR-203+scarmbled or **anti-miR-203+shZEB1** after treatment of radiation. The same tumor, differing in horizontal elongation, illustrates two conditions. ![file] ,