The Effect Of Small Nucleolar RNA SNORA11 On The Proliferation And Migration Of Breast Cancer Cell And Its Molecular Mechanism

Objective: Breast cancer ranks first among malignant tumors,which seriously hurts the physical and psychological health of breast cancer patients.It has become a difficult research problem because of its complex classification and tumor heterogeneity.With the rapid development of high-throughput sequencing technology and bioinformatics,small nucleolar RNA have gradually come to people’s view and have been found to be involved in tumorigenesis,tumor suppression,regulation of cell cycle mechanisms(such as apoptosis and cell growth),tumor markers,regulation of epithelial-mesenchymal transition,epigenetic and genetic functions of cells.It also plays an important biological role in cellcell communication with the help of exosomes.Small nucleolar RNA has also been found to play a role in tumor development and functional regulation.Further exploring the functional mechanism of sno RNAs can provide a new perspective for the diagnosis and treatment of breast cancer.Methods: In this study,small nucleolar RNA SNORA11 with differential expression was screened out since we obtained RNA-Se Q data from 1071 breast cancer patients and113 normal breast tissues in the TCGA database.The basic expression was verified by normal breast cells MCF-10 A and breast cancer cell lines MCF-7,T-47 D,BT-549 and MDA-MB-231.The expression of SNORA11 in breast cancer was detected at the tissue level based on 16 pairs of cancer and adjacent fresh frozen tissues and 16 paraffin sections of breast cancer.Overexpressed and silenced cell models were constructed in breast cancer MCF-7 and MDA-MB-231 cell lines,and the effects of SNORA11 on proliferation of breast cancer cells were detected by CCK-8 proliferation assay and plate clonal colony formation assay.transwell migration test and scratch healing test examined the effects of SNORA11 on migration ability of breast cancer cells.Finally,Western blot test was used to detect the changes of β-catenin and Snail protein expression levels after SNORA11 was expressed and silenced,and to verify whether SNORA11 regulates the proliferation and migration of breast cancer cells through β-catenin/Snail pathway.Results:In the TCGA database,SNORA11 was highly expressed in breast cancer compared with normal breast tissue(p=3.5e-7).Compared with breast epithelial cells MCF-10 A,SNORA11 was highly expressed in breast cancer cell lines MCF-7,T-47 D,MDA-MB-231 and BT-549.It was further verified that SNORA11 was highly expressed in 16 pairs of clinical breast cancer fresh tissues and adjacent tissues.The absorbance of MCF-7 and MDA-MB-231 cells overexpressed with SNORA11 was higher than that in oe-NC group(p<0.05,p<0.05),but the absorbance of MCF-7 and MDA-MB-231 cells silenced with SNORA11 was lower than that in control group(p<0.05,p<0.05).MCF-7and MDA-MB-231 groups transfected with oe-SNORA11 formed more colonies than the control group(p<0.05,p<0.05),while the clonal formation rate of MCF-7 and MDA-MB-231 cells transfected with ASO-SNORA11 was lower than that of the control group(p<0.01,p<0.05).The proportion of healing area of MCF-7 and MDA-MB-231 overexpressed SNORA11 was higher than that of the control group(p<0.05,p<0.05),while the healing speed of MCF-7 and MDA-MB-231 in silenced SNORA11 was slower than that in the control group(p<0.05,p<0.05).The number of cells migrating to transwell in MCF-7 and MDA-MB-231 overexpressed SNORA11 was higher than that in control group(p<0.01,p<0.05),while the migration ability of MCF-7 and MDA-MB-231 in silenced SNORA11 was lower than that in control group(p<0.05,p<0.01).The β-catenin and Snail expressions in MCF-7 and MDA-MB-231 cells overexpressed SNORA11 were higher than those in control group(p<0.05,p<0.05).β-catenin and Snail expression in MCF-7 and MDA-MB-231 cells silenced SNORA11 decreased compared with control group(p<0.05,p<0.05).Conclusion:Small nucleolar RNA SNORA11 is highly expressed in breast cancer,and SNORA11 can increase the proliferation and migration ability of breast cancer cells.SNORA11 may promote the proliferation and migration of breast cancer cells through β-catenin/Snail pathway.