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

Cancer Biol Ther. 2018 Jul 3;19(7):590-597. doi: 10.1080/15384047.2018.1449610. Epub 2018 May 3.


Background: LncRNA PTCSC3 is a tumor suppressor in thyroid cancer, and its role in drug resistance of anaplastic thyroid cancer (ATC) to chemotherapy drug doxorubicin was investigated in this study.

Methods: Expression of RNA and protein was analyzed by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze the expression rate of CD133+ cells. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. Combination condition and interaction between PTCSC3 and STAT3 were determined by RIP and RNA pull-down assay, respectively. MTT assay was performed to detect cytotoxicity. Chromatin immunoprecipitation was conducted to identify interactions between STAT3 and DNA promoter of INO80.

Results: LncRNA PTCSC3 was low-expressed in ATC tissues and cells. Over-expressed PTCSC3 inhibited the drug resistance of ATC to doxorubicin. PTCSC3 negatively regulated STAT3, and STAT3 promoted expression of INO80. PTCSC3 regulated INO80 through STAT3. PTCSC3 suppressed stem cells properties and drug resistance of ATC to doxorubicin.

Conclusion: LncRNA PTCSC3 inhibits INO80 expression by negatively regulating STAT3, and thereby attenuating drug resistance of ATC to chemotherapy drug doxorubicin.

Keywords: ATC; PTCSC3; STAT3; doxorubicin; drug resistance.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / therapeutic use
  • Cell Line, Tumor
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA-Binding Proteins
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Promoter Regions, Genetic / genetics
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / genetics
  • Thyroid Carcinoma, Anaplastic / drug therapy
  • Thyroid Carcinoma, Anaplastic / genetics*
  • Thyroid Carcinoma, Anaplastic / pathology
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / drug therapy
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology


  • Antibiotics, Antineoplastic
  • DNA-Binding Proteins
  • Ptcsc3 untranslated RNA, human
  • RNA, Untranslated
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Doxorubicin
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • INO80 protein, human