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

Research output: Contribution to journalArticlepeer-review

56 Citations (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'.

Original languageEnglish
Pages (from-to)101-106
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number3-5
Publication statusPublished - 2012 Sept


  • Breast cancer
  • LIN28
  • LIN28B
  • let-7

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


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