LIN28: A regulator of tumor-suppressing activity of let-7 microRNA in human breast cancer

Minako Sakurai, Yasuhiro Miki, Mariko Masuda, Shuko Hata, Yukiko Shibahara, Hisashi Hirakawa, Takashi Suzuki, Hironobu Sasano

研究成果: Article査読

51 被引用数 (Scopus)


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. This article is part of a Special Issue entitled 'Steroids and cancer'.

ジャーナルJournal of Steroid Biochemistry and Molecular Biology
出版ステータスPublished - 2012 9

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子医療
  • 分子生物学
  • 内分泌学
  • 臨床生化学
  • 細胞生物学


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