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Updated: Jul 13, 2026

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
11:29

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

LIN28B promotes the development of neuroendocrine prostate cancer

Jessica Lovnicki1, Yu Gan1,2, Tingting Feng1,3

  • 1Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

The Journal of Clinical Investigation
|July 8, 2020
PubMed

Insights

Therapy-induced neuroendocrine prostate cancer (t-NEPC) develops through the LIN28B/let-7/SOX2 pathway, which drives stem-like cell characteristics. Targeting LIN28B may offer a new therapeutic strategy for aggressive t-NEPC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Stem Cells

Background:

  • Therapy-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype with poor outcomes.
  • t-NEPC development may involve cancer stem-like cell signaling and lineage redifferentiation.
  • The role of core pluripotency genes like LIN28 and SOX2 in t-NEPC is not well understood.

Purpose of the Study:

  • To investigate the role of LIN28B and SOX2 in the development of therapy-induced neuroendocrine prostate cancer.
  • To elucidate the molecular mechanisms underlying t-NEPC progression driven by stem-like signaling.

Main Methods:

  • Analysis of LIN28B and SOX2 expression in t-NEPC patient tumors, xenografts, and cell models.
  • Immunohistochemistry to validate protein expression levels.
  • CRISPR-mediated gene depletion to assess LIN28B function.
  • Investigation of the LIN28B/let-7 miRNA/HMGA2/SOX2 regulatory axis.

Main Results:

  • LIN28B and SOX2 were co-upregulated in various t-NEPC models and patient biopsies.
  • LIN28B promoted stem-like gene networks, neuroendocrine biomarkers, and cell morphology.
  • LIN28B depletion inhibited t-NEPC tumorigenesis and xenograft growth.
  • LIN28B's function was mediated by suppressing let-7 miRNA, leading to HMGA2 and SOX2 de-repression.

Conclusions:

  • The LIN28B/let-7/SOX2 axis is a key mechanism driving t-NEPC development by regulating cancer stem-like cell networks.
  • LIN28B plays a critical role in t-NEPC progression.
  • LIN28B represents a potential therapeutic target for therapy-induced neuroendocrine prostate cancer.
Keywords:
OncologyProstate cancerUrology

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