title: LIN28: a regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer.
abstract: A tumor-suppressor gene, let-7 microRNA (miRNA) family, is often inactivated in various human malignancies. LIN28 is a RNA-binding protein that has been well characterized for regulation of let-7 maturation in undifferentiated embryonic stem cells at post-transcriptional level. Oncogenic regulation of let-7 miRNAs has been demonstrated in several human malignancies but their correlation with LIN28 has not been studied in breast cancer. We therefore explored a possible mechanism of tumorigenesis in breast carcinoma tissue via an alternation of let-7 miRNA precursor processing by LIN28 in this study. A total of 26 breast cancer surgical pathology specimens were evaluated for LIN28 and LIN28B expression using immunohistochemistry. We then isolated carcinoma cells in 21 cases using laser capture microdissection, and the miRNAs from these samples were profiled using PCR array analysis. LIN28 status was positively correlated with ERα, PR, and Ki-67 status and inversely correlated with HER2 status. These results suggest the possible involvement of LIN28 in regulation of sex steroid dependent cell proliferation of breast carcinoma cells. We further demonstrated that expression of let-7a, let-7c, let-7d (P=0.026) and let-7f (P=0.016) were inversely correlated with those of LIN28. These results also suggest that LIN28 promotes tumorigenic activity by suppressing let-7 miRNA maturation in breast carcinoma cells.
authors.affiliation: Department of Pathology, Tohoku University, Graduate School of Medicine, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Sakurai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Mariko
authors.initials: M
authors.lastname: Masuda
authors.forename: Shuko
authors.initials: S
authors.lastname: Hata
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shibahara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D061346:Laser Capture Microdissection; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; C516326:LIN28B protein, human; C000715187:Lin28A protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D011980:Receptors, Progesterone; C487931:mirnlet7 microRNA, human