Expression Of BMP7 In Cervical Cancer And Inhibition Of Epithelial-Mesenchymal Transition By BMP7 Knockdown In HeLa Cells

Background:Cervical cancer is the most common female reproductive tract malignant tumor,its morbidity and mortality rank first in female reproductive tract malignant tumors all over the world.The major risk factor of cervical cancer is persistent high-risk human papillomavirus infection.Clinically,radical surgery,supplemented radiotherapy or radiotherapy combined with cisplatin-based chemotherapy is the main treatment method.However,advanced cervical cancer cannot be completely removed,has the characteristics of high recurrence rate,poor prognosis,local invasion and distant metastasis,and poor curative effect.Finding other effective treatments is important.The BMP family,especially BMP7,has been proved to regulate the proliferation,invasion and migration of cancer cells in the studies of various malignant tumors,but its expression and significance in cervical have not been confirmed.Objective:To investigate the expression and clinical significance of BMP7 in cervical cancer tissues.To investigate the role of BMP7 on the proliferation,invasion and migration of cervical cancer HeLa cells.Methods:The expression of BMP7 in cervical tissues,paracancerous tissues and benign or precancerous lesions was detected by immunohistochemistry and compared.Lentivirus transfected to knock down the expression of BMP7 in HeLa cells.Western blot was used to verify the knock down of BMP7,and then detect the effect of BMP7 knocking down on the expression of smad1/5/9 and p-smad1/5/9(a factor of the BMP7/Smad signaling pathway).Using Western blot to investigate the expression of epithelial-mesenchymal transition(EMT)related proteins epithelial-cadherin(E-cadherin),neural-cadherin(N-cadherin),Vimentin,Snail and Slug.Cell Counting Kit-8 was used to detect cell proliferation.Transwell migration and invasion assays were performed to measure cell invasion and migration.The cell cycle was detected by flow cytometry.Results:The expression of BMP7 in cervical cancer tissues was statistically increased compared with the paracancerous tissues(P<0.0001).Compared with normal cervical epithelial tissues,the positive expression of BMP7 in cancer tissues was statistically increased(P<0.0001).There was no significant difference in the expression of BMP7 in different cervical cancer tissues in FIGO stage or pathological grade.After lentivirus transfected and knocked down the expression of BMP7 in HeLa cells,the expression of smad 1/5/9 protein was not significantly changed,but the expression of p-smad 1/5/9 protein was significantly decreased(p<0.05).Expression of EMT-related proteins N-cadherin(P<0.01),Vimentin(P<0.001),Snail and Slug(P<0.01)was decreased,while E-cadherin(P<0.01)was increased.Downregulation of BMP7 in HeLa cells caused a decrease of the cell proliferation rate(P<0.05),G1 cell cycle arrest(P<0.01),and decrease of cell invasion and migration ability(P<0.01).Conclusion:BMP7 expression in cervical cancer tissues was significantly increased,the expression of BMP7 may play a role in the development of cervical cancer.The knockdown of BMP7 in cervical cancer HeLa cells inhibited cell proliferation,migration and invasion,resulted in G1 cell cycle arrest and reversed the EMT process.These effects may be due to the blocking of the BMP7/smad 1/5/9 signaling pathway.