Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jul 3;19(7):590-597.
doi: 10.1080/15384047.2018.1449610. Epub 2018 May 3.

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

Xiao-Ming Wang  1   2 , Yang Liu  1   2 , Yu-Xia Fan  1   2 , Zheng Liu  1   2 , Qing-Ling Yuan  1   2 , Meng Jia  1   2 , Zu-Shi Geng  1   2 , Ling Gu  1 , Xiu-Bo Lu  1   2
Affiliations

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

Xiao-Ming Wang et al. Cancer Biol Ther. .

Abstract

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
LncRNA PTCSC3 was low-expressed in ATC tissues. (A) The expression of PTCSC3 in FTC (n = 20) and ATC tissues (n = 20) was quantified by qRT-PCR. **P < 0.01 vs. FTC; the expression of proteins was analyzed by western blot. (B) The positive expression rate of CD133 was analyzed by flow cytometry. **P < 0.01 vs. FTC; the levels of ALDH and MDR-1 were analyzed by western blot.
Figure 2.
Figure 2.
LncRNA PTCSC3 was low-expressed in ATC cells. (A) The expression of PTCSC3 in FTC 238, FTC 133 and 8505C cells was quantified by qRT-PCR. **P < 0.01 vs. FTC 238; the expression of proteins was analyzed by western blot. (B) The positive expression rate of CD133 in FTC 238, FTC 133 and 8505C cells was analyzed by flow cytometry. **P < 0.01 vs. FTC 238; the levels of ALDH and MDR-1 were analyzed by western blot.
Figure 3.
Figure 3.
Over-expressed PTCSC3 inhibited the drug resistance of ATC. (A) The cytotoxicity of DOX to FTC 238 and FTC 133 was detected by MTT assay. **P < 0.01 vs. si-control. (B) The cytotoxicity of DOX to 8505C was detected by MTT assay. **P < 0.01 vs. pcDNA.
Figure 4.
Figure 4.
LncRNA PTCSC3 negatively regulated STAT3. (A) Combination condition between PTCSC3 and STAT3 was determined by RIP assay. (B) The interaction between PTCSC3 and STAT3 was detected by RNA pull-down assay. **P < 0.01, vs. IgG. (C) The expression of STAT3 was analyzed by western blot. (D) The expression of STAT3 mRNA in 8505C cells was quantified by qRT-PCR. (E) The expression of STAT3 in 8505C cells was analyzed by western blot. *P < 0.05 vs. pcDNA; **P < 0.01 vs. pcDNA.
Figure 5.
Figure 5.
STAT3 promoted expression of INO80. (A) The chromatin immune-precipitation was used to verify the binding between PTCSC3 and the promoter of STAT3. (B) The expression levels of INO80 mRNA and protein in FTC238 cells were examined by qRT-PCR and western blot, respectively. **P < 0.01 vs. pcDNA. (C) The expression levels of INO80 mRNA and protein in 8505C cells were examined by qRT-PCR and western blot, respectively. **P < 0.01 vs. si-control.
Figure 6.
Figure 6.
LncRNA PTCSC3 regulated INO80 through STAT3. (A) The expression levels of INO80 mRNA and protein in FTC238 cells were examined by qRT-PCR and western blot, respectively. **P < 0.01 vs. si-control. ##P < 0.01 vs. si-PTCSC3. (B) The expression levels of INO80 mRNA and protein in 8505C cells were examined by qRT-PCR and western blot, respectively. **P < 0.01 vs. pcDNA. ##P < 0.01 vs. pcDNA-PTCSC3.
Figure 7.
Figure 7.
LncRNA PTCSC3 suppressed stem cells characteristics and drug resistance of ATC. (A) The positive expression rate of CD133 was analyzed by flow cytometry. *P < 0.05 vs. si-control; #P < 0.05 vs. si-PTCSC3; The cytotoxicity of DOX to FTC238 was detected by MTT assay. **P < 0.01 vs. si-control; ##P < 0.01 vs. si-PTCSC3; the levels of MDR-1 was analyzed by western blot. (B) The positive expression rate of CD133 was analyzed by flow cytometry. **P < 0.01 vs. pcDNA; ##P < 0.01 vs. pcDNA-PTCSC3; The cytotoxicity of DOX to FTC238 was detected by MTT assay. **P < 0.01 vs. pcDNA; ##P < 0.01 vs. pcDNA-PTCSC3; the levels of MDR-1 was analyzed by western blot.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Carling T, Udelsman R. Thyroid cancer. Annu Rev Med. 2014;65:125–37. doi:10.1146/annurev-med-061512-105739. PMID:24274180. - DOI - PubMed
    1. Maniakas A, Forest VI, Jozaghi Y, Saliba J, Hier MP, Mlynarek A, Tamilia M, Payne RJ. Tumor classification in well-differentiated thyroid carcinoma and sentinel lymph node biopsy outcomes: a direct correlation. Thyroid. 2014;24(4):671–4. doi:10.1089/thy.2013.0160. PMID:24199963. - DOI - PubMed
    1. Haddad RI, Lydiatt WM, Ball DW, Busaidy NL, Byrd D, Callender G, Dickson P, Duh QY, Ehya H. Anaplastic Thyroid Carcinoma, Version 2.2015. J Natl Compr Canc Netw. 2015;13(9):1140–50. doi:10.6004/jnccn.2015.0139. PMID:26358798. - DOI - PMC - PubMed
    1. Zheng X, Cui D, Xu S, Brabant G, Derwahl M. Doxorubicin fails to eradicate cancer stem cells derived from anaplastic thyroid carcinoma cells: characterization of resistant cells. Int J Oncol. 2010;37(2):307–15. PMID:20596658. - PubMed
    1. Decaussin-Petrucci M, Deladoëy J, Hafdi-Nejjari Z, Sassolas G, Borson-Chazot F, Abu-Khudir R, Fusco A, Descotes F, Cournoyer S, Sartelet H. Expression of CD133 in differentiated thyroid cancer of young patients. J Clin Pathol. 2015;68(6):434–40. doi:10.1136/jclinpath-2014-202625. PMID:25770162. - DOI - PubMed

MeSH terms