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LncRNA PTCSC3 affects drug resistance of anaplastic thyroid cancer through STAT3/INO80 pathway

Xiao-Ming Wang1,2, Yang Liu1,2, Yu-Xia Fan1,2

  • 1a Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University , Zhengzhou , China.

Cancer Biology & Therapy
|March 22, 2018
PubMed
Abstract

Insights

Long non-coding RNA PTCSC3 acts as a tumor suppressor in anaplastic thyroid cancer (ATC). Overexpression of PTCSC3 reduces doxorubicin resistance by inhibiting INO80 expression via STAT3 regulation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Anaplastic thyroid cancer (ATC) is an aggressive thyroid cancer subtype.
  • Drug resistance to chemotherapy, such as doxorubicin, is a major challenge in ATC treatment.
  • Long non-coding RNAs (lncRNAs) play critical roles in cancer development and progression.

Purpose of the Study:

  • To investigate the role of lncRNA PTCSC3 in the drug resistance of ATC to doxorubicin.
  • To elucidate the molecular mechanism underlying PTCSC3's function in ATC drug resistance.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and Western blot for gene and protein expression analysis.
  • Flow cytometry to assess CD133+ cell expression.
  • Recombinant plasmid transfection and cell transfection to modulate gene expression.
  • RNA immunoprecipitation (RIP) and RNA pull-down assays to determine interactions.
  • MTT assay for cytotoxicity assessment.
  • Chromatin immunoprecipitation (ChIP) to identify STAT3-DNA promoter interactions.

Main Results:

  • LncRNA PTCSC3 was found to be lowly expressed in ATC tissues and cells.
  • Overexpression of PTCSC3 significantly inhibited doxorubicin resistance in ATC.
  • PTCSC3 negatively regulated STAT3, which in turn promoted INO80 expression.
  • PTCSC3 suppressed stem cell properties and doxorubicin resistance in ATC by regulating INO80 through STAT3.

Conclusions:

  • LncRNA PTCSC3 acts as a tumor suppressor in ATC.
  • PTCSC3 inhibits INO80 expression by negatively regulating STAT3.
  • PTCSC3 attenuates doxorubicin resistance in ATC, offering a potential therapeutic target.
Keywords:
ATCPTCSC3STAT3doxorubicindrug resistance

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