TGIF2 promotes cervical cancer metastasis by negatively regulating FCMR
Authors: Z Deng
Z-M Li
M Dong
J Jiang
R-H Wu
H-L Zhou
D Kou
L-H Chen
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: TGIF2 expression; clinicopathological features; cervical cancer; FCMR; proliferation
Affiliations: Department of Gynecology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. .

Abstract:  Objective: We aimed at studying the correlation between TGIF2 expression and clinicopathological features of cervical cancer (CCa). The relationship between TGIF2 and FCMR and its influence on the proliferation and metastasis of tumor cells were investigated using molecular biology techniques, so as to reveal the pathogenesis of CCa and provide a new target for clinical treatment. Patients and methods: TGIF2 expression in 60 pairs of cervical tumors and paracancerous tissues samples collected from CCa patients of our hospital was studied by quantitative real-time polymerase chain reaction (qPCR) analysis, and the association between TGIF2 expression and the clinical indicators or prognosis of CCa patients were analyzed. CCa cells with TGIF2 knockdown were constructed using transfection technology. Changes in the biological phenotypes (proliferation, migration, invasion) of CCa cells C33-A and HeLa after TGIF2 knockdown were determined by Cell Counting Kit-8 (CCK-8) and transwell assays. In addition, the effects of TGIF2/FCMR axis on CCa metastasis were further explored in nude mice in vivo. Results: Our data revealed a significant increase in TGIF2 mRNA expression in CCa tissue specimens compared to adjacent ones, and the increasing degree was positively correlated with the incidence of lymph node or distant metastasis of CCa patients. The results of CCK-8 and transwell suggested that knocking down TGIF2 effectively attenuated the proliferative ability and invasiveness of CCa cells. Luciferase assay confirmed that TGIF2 can directly bind to the DNA promoter of its target gene FCMR. Simultaneous transfection of sh-TGIF2 and sh-FCMR partially reversed the inhibitory effect of single transfection of TGIF2 knockdown on the malignant progression of CCa. Experiments in nude mice also suggested that TGIF2 could promote CCa tumorigenesis through the modulation of FCMR expression. Conclusions: In summary, TGIF2 can promote the migration and proliferation ability of cervical cancer cells via down-regulating FCMR. Our study provides a new therapeutic target for the clinical treatment of cervical cancer. 

Retracted: No

PubPeer comments:
 From the Methods:  *A total of 60 pairs of CCa tissues and paracancerous tissues were collected January 2018 to January 2020 in our hospital. * The paper was published in June 2020, two years after enrolling the first patients, and half a year after enrolling the last ones. Yet, Figure 1D shows that the patients were followed for more than 5 years. How did the authors do this? And how can the progression-free plot on the right give higher survival rates than the death-free plot? According to the plots 80% of the High-TGIF2 groups is dead at 75 months, but only 70% experienced a progression of the disease. I would have expected the opposite, since death sort of qualifies as progression of the disease. ![file] ,