title: MicroRNA-204 targets JAK2 in breast cancer and induces cell apoptosis through the STAT3/BCl-2/survivin pathway.
abstract: MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-204 plays an important role in various human cancers. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated that miR-204 expression level was markedly reduced in both the human breast cancer tissue and cultured breast cancer cell lines (MCF-7, MDA-MB-231). Overexpression of miR-204 inhibited the proliferation and promoted the apoptosis in breast cancer cells, which were reversed by co-transfection of miR-204 inhibitor. We validated that Janus kinase 2 (JAK2), as a direct target of miR-204, is overexpressed in breast cancer. Knockdown of JAK2 suppressed cell viability and induced apoptosis in breast cancer cells. Moreover, the level of miR-204 is negatively correlated with p-STAT3 and anti-apoptotic genes BCl-2 and surviving in breast cancer. In conclusions, miR-204 targets JAK2 and suppressed JAK2 and p-JAK2 expression in breast cancer, which further inhibit the activation of STAT3, BCl-2 and survivin. These findings indicate that manipulation of miR-204 expression may represent a novel therapeutic strategy in the treatment of breast cancer.
authors.affiliation: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.
authors.forename: Xilong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.
authors.forename: Shujian
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical College Binzhou 256603, China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Yang
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000077022:Survivin; D013997:Time Factors; D014162:Transfection
chemical_list: C000595707:BCL2 protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: Breast cancer; JAK2; apoptosis; miR-204; proliferation