Tumor suppressor role of miR-133a in gastric cancer by repressing IGF1R
Authors: Li-Ming Tang
Jun Ren
Kun Liu
Yu Gong
Journal: World Journal of Gastroenterology (2015)
Discipline: CLINICAL MEDICINE
Keywords: Gastric cancer; Insulin-like growth factor 1 receptor; Tumor suppressor; miR-133a.
Affiliations: Yu Gong, Jun Ren, Kun Liu, Li-Ming Tang, Department of Gastrointestinal Surgery, Nanjing Medical University Affiliated Changzhou No. 2 People's Hospital, Changzhou 213000, Jiangsu Province, China.

Abstract:  Aim: To investigate the function and mechanism of miR-133a in gastric cancer (GC) and its relationship with clinicopathological characteristics of GC. Methods: A total of 105 GC patients who underwent surgical resection as primary treatment were selected for this study. Real-time quantitative reverse transcriptase polymerase chain (qRT-PCR) was used to examine the expression levels of miR-133a in human GC and adjacent non-tumor tissues, as well as in GC cell lines (SGC-7901, BGC-823, MGC-803, and AGS) and a human gastric mucosal epithelial cell line (GES-1). The biological role of miRNA (miR)-133a was assessed in the GC cell lines using MTT, apoptosis, migration and invasion, and colony formation assays, and xenograft tumorigenesis. qRT-PCR and western blot analyses were used to evaluate the potential target gene expression of miR-133a. Pearson's correlation was calculated to evaluate the correlation between miR-133a and insulin-like growth factor 1 receptor (IGF1R) expression. The regulation of IGF1R by miR-133a was verified using the luciferase reporter assay. Results: In 80% of the 105 GC patients, the mean expression of miR-133a was significantly downregulated in tumor tissues compared with adjacent normal tissues (1.215 ¬± 0.1477 vs 3.093 ¬± 0.4104, P &lt; 0.0001). Downregulation of miR-133a was significantly correlated with the degree of differentiation (P = 0.01), local invasion (P = 0.001) and TNM stage (P = 0.02) in GC patients. Compared with a control construct, forced expression of miR-133a in GC cell lines inhibited proliferation (0.4787 ¬± 0.0219 vs 0.7050 ¬± 0.0147, P = 0.0013 in SGC-7901 cells; and 0.5448 ¬± 0.0085 vs 0.7270 ¬± 0.0084, P = 0.001 in MGC-803 cells); migration (0.6333 ¬± 0.0233 vs 1.037 ¬± 0.0584, P = 0.003 in SGC-7901 cells; 0.6126 ¬± 0.0311 vs 1.024 ¬± 0.0456, P = 0.0017 in MGC-803 cells); and invasion (0.613 ¬± 0.0399 vs 1.033 ¬± 0.0278, P = 0.0013 in SGC-7901 cells; 0.7433 ¬± 0.0221 vs 1.017 ¬± 0.0311, P = 0.002 in MGC-803 cells). It also induced apoptosis (18.19% ¬± 0.2483% vs 5.887% ¬± 0.3837%, P &lt; 0.0001 in SGC-7901 cells; 22.69% ¬± 0.7846% vs 9.347% ¬± 0.3012%, P &lt; 0.0001 in MGC-803 cells). Furthermore, miR-133a inhibited tumor growth and xenograft tumorigenesis of SGC -7901 cells in vivo. In addition, we identified IGF1R as a regulatory target of miR-133a in GC. Conclusion: This study suggests that miR-133a is downregulated in GC and functions as a tumor suppressor in vitro and in vivo partly by repressing IGF1R. 

Retracted: No

PubPeer comments:
 *[left]* Fig 2. *[right]* Fig 3D E from [Ye, Liu Qian (2016)] .  The material shared with Ye, Liu Qian link the present paper to a network of mutually-plagiarised papers reconstructed by [a Chinese science-integrity enthusiast] , blogging in 2016 and citing work by the now-vanished site PlagiarismWatch. All were presumably products of the same papermill. Some of this series of retractions was [covered by RetractionWatch] .   , 
 Fig 4B.  Expression levels of miR-133a and IGF1R were inversely correlated. Please share my admiration for this scatter-plot of 105 purportedly-independent measurements.  ,