Abstract
BackgroundIt has been reported that lncRNA MAGI2-AS3 can promote many types of cancer, such as breast cancer and bladder cancer, by regulating cell behaviors, such a proliferation, invasion, and migration. However, its role in cervical squamous cell carcinoma (CSCC) is unclear. This study aims to investigate the role of MAGI2-AS3 in CSCC.MethodsSixty-four CSCC patients (36 to 68 years, 46.3 ± 5.1 years) out of 136 CSCC patients admitted by Shengjing hospital affiliated to China Medical University from June 2010 to October 2013 were included in the present study. Among the 64 enrolled patients, 20 were HPV-16 positive cases, 24 were HPV-18 positive cases and 20 were HPV negative. CSCC and non-tumor biopsies from CSCC patients as well as C-33A cell lines were used. Cells were transfected with MAGI2-AS3 and CDK6 expression vectors as well as with MAGI2-AS3 siRNA to analyze gene interactions. Cell cycle analysis was performed to analyze the effects of transfections on cell cycle progression. qPCR and western blot were applied to analyze gene expression. Paired t-test and ANOVA (one-way) combined with Tukey test were used for data comparisons. Survival analysis was performed by plotting and comparing survival curves.ResultsqRT-PCR results showed that CDK6 and MAGI2-AS3 were both up-regulated in CSCC and positively correlated with each other. MAGI2-AS3 and CDK6 expression was not significantly affected by HPV infections. High levels of MAGI2-AS3 were associated with the poor survival of CSCC patients. In CSCC cells, MAGI2-AS3 over-expression up-regulated CDK6, while MAGI2-AS3 siRNA down-regulated CDK6. In CCK-8 assay, MAGI2-AS3 and CDK6 over-expression led to increased proliferation rate of CSCC cells by reducing CDK6 levels, while MAGI2-AS3 siRNA didn’t. In addition, CDK6 over-expression attenuated the effect of MAGI2-AS3 siRNA silencing.ConclusionsIn conclusion, MAGI2-AS3 promoted CSCC cell proliferation by up-regulating CDK6.
Highlights
It has been reported that lncRNA MAGI2-AS3 can promote many types of cancer, such as breast cancer and bladder cancer, by regulating cell behaviors, such a proliferation, invasion, and migration
In vitro cell experiments showed that inhibition of CDK6 by its inhibitor LEE011 induced G1 phase arrest, thereby suppressing cancer cell proliferation in leukemia [10]
It is known that CDK6 activity can be regulated by long non-coding RNAs (> 200 nt, lncRNAs) [11], which are a group of RNA transcripts with no protein-coding capacity but able to regulate downstream gene expression to participate in cellular processes, such as transcription and DNA repair [12]
Summary
It has been reported that lncRNA MAGI2-AS3 can promote many types of cancer, such as breast cancer and bladder cancer, by regulating cell behaviors, such a proliferation, invasion, and migration. Its role in cervical squamous cell carcinoma (CSCC) is unclear. Cervical cancer is the 2nd most common type of gynecological tumors worldwide, and cervical squamous cell carcinoma (CSCC) accounts for 80–90% of cervical cancer [1, 2]. In vitro cell experiments showed that inhibition of CDK6 by its inhibitor LEE011 induced G1 phase arrest, thereby suppressing cancer cell proliferation in leukemia [10]. It has been reported that lncRNA MAGI2-AS3 regulated breast cancer cell proliferation through the modulation of Fas and Fas ligand [13]. This study aims to investigate the role of MAGI2-AS3 in CSCC
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