| Objective: To investigate the role of CBX7 in cervical cancer and its effect on chemotherapy drug sensitivity,and to demonstrate that CBX7 interferes with the occurrence of EMT,the progression of cervical cancer and the sensitivity of chemotherapy drug treatment in cervical cancer via regulating ITG?3/TGF?1 pathway through PI3K/AKT.Methods: Immunohistochemistry(IHC)was used to detect CBX7 and tumor related genes,and collect clinicopathological information retrospectively.The data were analyzed as follows: Differences of expression of CBX7 and tumor-related genes in CC and adjacent non-tumor tissues;the relationship of CBX7 with clinicopathological parameters and tumor related genes;the impact of CBX7 expression on the survival of patients.He La and Si Ha cells were stably transfected with Lentivirus vector system;Si Ha cells were exposed to cisplatin,and the transplanted tumor model was established by si CBX7 Si Ha cells.MTT and clone formation methods were used to detect cell proliferation;wound healing,Transwell assay were used to detect cell migration and invasion;flow cytometry was used to detect the apoptosis;IHC,q RT-PCR were used to detect CBX7 and tumor-related genes of transplanted tumor.RNAi was used to inhibit the ITG?3/TGF?1 axis of stably transfected cells.Above Si Ha cells were exposed to Cisplatin;cell proliferation,cell invasion,apoptosis were detected;Western blotting and q RT-PCR were used to detect the differences of m RNA,protein expression of these signaling pathway genes between transfection and non transfection sh RNA TGF?1.Results:(1)The expression of CBX7 was negatively correlated with clinical stage,lymph node metastasis,vessel invasion,and decreased with the histological grading;(2)CBX7 was positively correlated with CC survival rate;(3)IHC results showed that the positive expression rates of CBX7 in CC tissues were lower than those in adjacent non-tumorous tissues and negatively correlated with the expression of ITG?3,TGF?1,PI3 K,AKT,p-AKT and VIM,positively correlated with the expression of E-cad;(4)The biological behavior of stably transfected cells were detected,knockdown of CBX7 promoted the proliferation,migration and decreased the apoptotic ability;up-regulation of CBX7 increased the inhibition of proliferation and apoptotic effec of cisplatin on Si Ha cells;Knockdown of CBX7 increased the tumorigenesis rate,the volume and weight of transplanted tumor model in nude mice;(5)IHC analysis results showed that the positive expression rates of CBX7 and E-cad in si CBX7 group was lower than that in the control groups,while VIM has a reverse result;(6)m RNA expressions of ITG?3,TGF?1,PI3 K and AKT were higher in CBX7 silencing group than those in the control groups;(7)The cell biological behavior were detected after silenced TGF?1,the effect of proliferation promotion and apoptosis inhibition of si CBX7 were weakened by silencing TGF?1;(8)Knocking down CBX7 increased the m RNA and protein expressions of ITG?3,TGF?1,PI3 K,AKT,VIM,and decreased the expression of E-cad;Transfection with sh RNA TGF?1 reversed the increase of these m RNA and protein expressions(9)Si Ha cells were exposed to cisplatin,the overexpression of CBX7 lowered the m RNA and protein expression of ITG?3/TGF?1 signaling pathway and VIM,also increased E-cad.Conclusions: The expression of CBX7 is low in human CC tissues and it is one of the predictors of the prognosis of CC.Low expression of CBX7 promotes the proliferation,migration and invasion,inhibits the apoptosis of CC cells,the overexpression of CBX7 improves the sensitivity to chemotherapy drugs.si CBX7 regulates the EMT process of CC cells via ITG?3/TGF?1,and transfection with sh RNA TGF?1 can partially reverse the EMT characterization of CC cells.The study confirms that CBX7 is a tumor suppressor gene in cervical cancer.CBX7 may be a potential factor in the treatment of cervical cancer.Inhibition of ITG?3/TGF?1signaling pathway by CBX7 is likely to be a new treatment method to improve the efficacy of cervical cancer. |
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