黏蛋白5B上调高迁移率族蛋白组A1促进乳腺癌细胞侵袭转移

MUC5B upregulating HMGA1 promotes invasion of breast cancer cells

目的探讨黏蛋白5B(mucin 5B,MUC5B)抑制乳腺癌细胞侵袭转移的作用及可能的分子机制。方法在多个数据库中统计MUC5B在乳腺癌组织中的表达量,qRT-PCR方法检测MUC5B在正常乳腺上皮细胞和多种乳腺癌细胞中的表达量。在乳腺癌细胞中过表达和敲低MUC5B,transwell实验检测上述细胞的侵袭能力。生物信息学预测结合实验验证MUC5B对高迁移率族蛋白组A1(human high mobilitygroup A1,HMGA1)的调控作用。在乳腺癌细胞中干预MUC5B,同时干预MUC5B和HMGA1,transwell实验检测上述细胞的侵袭能力。结果UALCAN结合The human Protein Altas在线数据库证实MUC5B在乳腺癌组织中的表达量显著高于其在正常组织中的表达量。qRT-PCR结果显示MUC5B在乳腺癌中的表达量远高于其在正常上皮细胞MCF-10A中的表达量。在乳腺癌细胞MCF-7中过表达MUC5B,transwell实验发现MUC5B可明显增加该细胞的侵袭能力;在乳腺癌细胞MDA-MB-231中敲低MUC5B,则该细胞的侵袭能力大大降低。最后,生物信息学结合qRT-PCR和WB实验证实MUC5B可显著上调HMGA1的表达。在MCF-7细胞中,敲低HMGA1可逆转该细胞因MUC5B而增加的侵袭能力;相似的,在MDA-MB-231细胞中,过表达HMGA1可逆转该细胞因敲低MUC5B而减弱的侵袭能力。结论MUC5B通过上调HMGA1促进乳腺癌细胞侵袭。

Objective To explore the function and mechanism of MUC5B in invasion of breast cancer cells.Methods Several databanks were used to predict MUC5B expression in breast cancer tissues,and qRTPCR assays were performed to measure MUC5B expression in normal epithelial cell and different types of breast cancer cells.overexpress MUC5B in MCF-7 cells,and down-regulate MUC5B in MDA-MB-231 cells,and invasion ability of the cells was detected via transwell assays.The relationship between MUC5B and HMGA1 was predicted through starbase databank.qRT-PCR and WB assays were carried out to evaluate HMGA1 expression in breast cancer cells with interfering MUC5B.Transwell assays were utilized in MCF-7 cells with overexpressing MUC5B,in MCF-7 cells with overexpressing MUC5B and inhibiting HMGA1.Like the same,MDA-MB-231 cells with inhibiting MUC5B,MDA-MB-231 cells with inhibiting MUC5B and overexpressing HMGA1,these cells invasion were also conducted by transwell assays.Results Online databank suggested that MUC5B was increased in breast cancer tissues than that in normal tissues.The similar results were found in normal epithelial cell and breast cancer cells.Gain-of-function and lose-of-function assays showed that MUC5B promoted the invasion of breast cancer cells.Bioinformatics analysis combined with qRT-PCR and WB assays demonstrated that MUC5B significantly enhanced HMGA1 expression.Down-regulated HMGA1 could reverse the effect of increased MUC5B on MCF-7 invasion.Similarly,overexpressed HMGA1 could reverse the effect of down-regulated MUC5B on MDA-MB-231 cells invasion.Conclusion MUC5B upregulated HMGA1 to accelerate breast cancer cells invasion.