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Long Non-coding RNA CCAT1 Acts as an Oncogene and Promotes Sunitinib Resistance in Renal Cell Carcinoma

Liping Shan1, Wei Liu2, Yunhong Zhan1

  • 1Department of Urology, Shengjing Hospital, China Medical University, Shenyang, China.

Frontiers in Oncology
|October 19, 2020
PubMed

Insights

Long non-coding RNA CCAT1 promotes resistance to sunitinib in metastatic renal cell carcinoma by regulating c-Myc. Targeting CCAT1 may improve sunitinib therapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Sunitinib is a key treatment for metastatic renal cell carcinoma (mRCC), but resistance limits its efficacy.
  • Mechanisms underlying sunitinib resistance in mRCC require further elucidation.

Purpose of the Study:

  • To investigate the role of long non-coding RNA colon cancer-associated transcript-1 (lncRNA CCAT1) in sunitinib resistance in mRCC.
  • To explore the potential of targeting lncRNA CCAT1 to overcome sunitinib resistance.

Main Methods:

  • Comparison of lncRNA CCAT1 expression in sunitinib-resistant versus sensitive mRCC cells and patient samples.
  • Functional assays including cell growth, colony formation, and apoptosis after CCAT1 knockdown or overexpression.
  • Investigation of the interaction between CCAT1 and c-Myc.
  • Validation in a sunitinib-resistant ACHN mouse model.

Main Results:

  • lncRNA CCAT1 was significantly overexpressed in sunitinib-resistant mRCC cells and patient samples.
  • CCAT1 knockdown suppressed cell proliferation, colony formation, and induced apoptosis, effects reversed by c-Myc.
  • CCAT1 regulated the expression of anti-apoptotic proteins Bcl-2 and Mcl-1 via c-Myc.
  • CCAT1 knockdown enhanced sunitinib response in a preclinical mouse model.

Conclusions:

  • lncRNA CCAT1 promotes sunitinib resistance in renal cell carcinoma through a c-Myc-dependent pathway.
  • Targeting lncRNA CCAT1 represents a potential therapeutic strategy to improve sunitinib treatment outcomes in mRCC.
Keywords:
CCAT1apoptosisrenal cell carcinomaresistancesunitinib

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