title: miR-520b regulates migration of breast cancer cells by targeting hepatitis B X-interacting protein and interleukin-8.
abstract: MicroRNAs play important roles in tumor metastasis. Recently, we reported that the level of miR-520b is inversely related to the metastatic potential of breast cancer cells. In this study, we investigated the role of miR-520b in breast cancer cell migration. We found that miR-520b suppressed the migration of breast cancer cells with high metastatic potential, including MDA-MB-231 and LM-MCF-7 cells, although the inhibition of miR-520b enhanced the migration of low metastatic potential MCF-7 cells. We further discovered that miR-520b directly targets the 3'-untranslated region (3'UTR) of either hepatitis B X-interacting protein (HBXIP) or interleukin-8 (IL-8), which has been reported to contribute to cell migration. Surprisingly, tissue array assays showed that 75% (38:49) and 94% (36:38) of breast cancer tissues and metastatic lymph tissues, respectively, were positive for HBXIP expression. Moreover, overexpression of HBXIP was able to promote the migration of MCF-7 cells. Interestingly, HBXIP was able to regulate IL-8 transcription by NF-κB, suggesting that the two target genes of miR-520b are functionally connected. In addition, we found that miR-520b could indirectly regulate IL-8 transcription by targeting HBXIP. Thus, we conclude that miR-520b is involved in regulating breast cancer cell migration by targeting HBXIP and IL-8 via a network in which HBXIP promotes migration by stimulating NF-κB-mediated IL-8 expression. These studies point to HBXIP as a potential therapeutic target for breast cancer.
authors.affiliation: Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Jianli
authors.initials: J
authors.lastname: Zhang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Cui
authors.forename: Guangyao
authors.initials: G
authors.lastname: Kong
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Yue
authors.forename: Xiao
authors.initials: X
authors.lastname: Bai
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weiying
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.forename: Lihong
authors.initials: L
authors.lastname: Ye
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C508606:CXCL8 protein, human; D016209:Interleukin-8; C110719:LAMTOR5 protein, human; D035683:MicroRNAs; D016328:NF-kappa B; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm