title: Lin28 mediates radiation resistance of breast cancer cells via regulation of caspase, H2A.X and Let-7 signaling.
abstract: Resistance to radiation therapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to breast tumorigenesis; however, the relationship between Lin28 and radioresistance remains unknown. In this study, we investigated the association of Lin28 with radiation resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines. The results showed that the expression level of Lin28 was closely associated with resistance to radiation treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to radiation than MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which have low-level Lin28 expression. Transfection with Lin28 siRNA significantly led to an increase of sensitivity to radiation. By contrast, stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to radiation treatment. Stable expression of Lin28 also significantly inhibited radiation-induced apoptosis. Moreover, further studies have shown that caspases, H2A.X and Let-7 miRNA were the molecular targets of Lin28. Stable expression of Lin28 and treatment with radiation induced H2AX expression, while inhibited p21 and γ-H2A.X. Overexpression of Let-7 enhanced the sensitivities to radiation in breast cancer cells. Taken together, these results indicate that Lin28 might be one mechanism underlying radiation resistance, and Lin28 could be a potential target for overcoming radiation resistance in breast cancer.
authors.affiliation: Key Laboratory of Biotherapy of Zhejiang Province, Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Yuan
authors.forename: Kezhen
authors.initials: K
authors.lastname: Lv
authors.forename: Shuduo
authors.initials: S
authors.lastname: Xie
authors.forename: Peifen
authors.initials: P
authors.lastname: Fu
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Liu
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Chen
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.forename: Wuguo
authors.initials: W
authors.lastname: Deng
authors.forename: Wenxian
authors.initials: W
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D001943:Breast Neoplasms; D002470:Cell Survival / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000502:physiology*; D011836:Radiation Tolerance; D015398:Signal Transduction
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C468783:H2AX protein, human; D006657:Histones; C000715187:Lin28A protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C487931:mirnlet7 microRNA, human