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. 2023 Nov:71:101003.
doi: 10.1016/j.drup.2023.101003. Epub 2023 Sep 2.

CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification

Yangyang Zhan  1 , Yang Liu  2 , Rui Yang  3 , Qiong Chen  4 , Fei Teng  5 , Yueying Huang  1 , Xin Jiang  3 , Yueming Wang  4 , Bin Yu  6 , Ding Zhang  7 , Leilei Bao  8 , Xinli Liu  9 , Jiwei Huang  10
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CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification

Yangyang Zhan et al. Drug Resist Updat. 2023 Nov.

Abstract

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.

Keywords: CcRCC; CircPTEN; DNMT1; METTL3; MTOR inhibitors; PTEN.

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Conflict of interest statement

Declaration of Competing Interest We declare that the article we submitted on Drug resistance updates has not been published previously, that it is not under consideration for publication elsewhere, that its publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder.

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