Suppressing Dicer inhibits proliferation and contributes to cellular senescence, partially via a p21-associated

Chao-Wen Cheng1,2, Wen-Fang Fang3, Yea-Mey Yang1

  • 1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Insights

Dicer enzyme is upregulated in well-differentiated thyroid carcinoma (WDTC). Suppressing Dicer inhibits cancer cell proliferation and progression, partly via p21-dependent cell senescence and genomic instability.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Dicer is recognized for its role in micro (mi)RNA biosynthesis.
  • Its specific involvement in thyroid carcinogenesis remains largely unexplored.

Purpose of the Study:

  • To investigate the role of Dicer in the development of well-differentiated thyroid carcinoma (WDTC).
  • To evaluate the impact of Dicer inhibition on thyroid cancer cell behavior.

Main Methods:

  • Analysis of Dicer messenger RNA (mRNA) and protein levels in thyroid cancer tissues and cell lines.
  • Experimental silencing of Dicer1 in papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and normal thyroid cell lines.
  • Assessment of cell proliferation, cell-cycle progression, p21 expression, and markers of genomic instability (phospho-H2AX, BrdU incorporation).

Main Results:

  • Dicer1 mRNA was elevated in PTC, and Dicer protein was overexpressed in both PTC and FTC tissues.
  • Dicer suppression inhibited cell proliferation and repressed cell-cycle progression in thyroid cancer cell lines.
  • p21 expression increased, and genomic instability markers were observed upon Dicer knockdown.

Conclusions:

  • Dicer expression is elevated in WDTC.
  • Dicer plays a significant role in regulating the proliferative capacity of normal and WDTC cells.
  • Dicer influences cell senescence and genomic stability, at least partially through p21-dependent pathways.

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