Targeted Silencing of S100A8 Gene by miR-24 to Increase Chemotherapy Sensitivity of Endometrial Carcinoma Cells to Paclitaxel.
BACKGROUND The objective of this study was to determine whether miR-24 can regulate malignant proliferation and chemotherapy sensitivity of EC cells by targeted silencing of the S100 Calcium Binding Protein A8 (S100A8) gene. MATERIAL AND METHODS The expression of miR-24 in EC tissues was detected by quantitative real-time PCR. The proliferation ability and chemotherapy sensitivity were analyzed by MTT assay. Bioinformatics software was used to predict some potential target genes of miR-24. Luciferase activity assay was used to verify the relationship between target genes and miR-24. S100A8 protein expression was detected by Western blot analysis. RESULTS The low expression of miR-24 in EC tissues compared with normal control tissues suggests miR-24 might play a role in tumorigenesis of EC. EC HEC-1A cells were transfected with miR-24 agonist (agomiR-24) to up-regulate the expression of miR-24. Up-regulation of miR-24 inhibited the cell proliferation and advanced the chemotherapy sensitivity to paclitaxel in HEC-1A cells significantly. We used several types of bioinformatic software to predict that miR-24 could specifically combine with the 3' untranslated region (3'UTR) of the S100A8 gene, and this prediction was verified by Western blot and luciferase activities assay. The regulation effects of miR-24 enhancement on cell proliferation and chemotherapy sensitivity were largely reversed by S100A8 up-regulation. CONCLUSIONS miR-24 acts as a tumor-suppressing gene to inhibit malignant proliferation and advance chemotherapy sensitivity to paclitaxel in EC by targeted silencing of the S100A8 gene.
School of Health Sciences, Macao Polytechnic Institute, Macao, China (mainland).
Bin
B
Lang
Department of Neurobiology, China Medical University, Shenyang, Liaoning, China (mainland).
Chao
C
Shang
School of Health Sciences, Macao Polytechnic Institute, Macao, China (mainland).
Lirong
L
Meng
D020413:3' Untranslated Regions; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D040501:Calgranulin A / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D005260:Female; D020868:Gene Silencing; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; D040501:Calgranulin A; C543845:MIRN24 microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel