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. 2025 Jun 28:620:217639.
doi: 10.1016/j.canlet.2025.217639. Epub 2025 Mar 14.

CircRUNX1 enhances the Warburg effect and immune evasion in non-small cell lung cancer through the miR-145/HK2 pathway

Jinyou Li  1 , Shiwei Xu  1 , Yangyang Zhan  2 , Xinyi Lv  3 , Zhenyu Sun  1 , Li Man  4 , Donghua Yang  5 , Yahong Sun  6 , Shengguang Ding  7
Affiliations

CircRUNX1 enhances the Warburg effect and immune evasion in non-small cell lung cancer through the miR-145/HK2 pathway

Jinyou Li et al. Cancer Lett. .

Abstract

Non-small cell lung cancer (NSCLC) is acknowledged as the primary subtype of lung cancer. The Warburg effect, marked by elevated glucose consumption and lactate fermentation, is a prevalent characteristic of NSCLC. The mechanisms by which circRNA mediates the regulation of the Warburg effect and immune evasion in NSCLC remain unclear. This study found an elevated circRNA, circRUNX1, whiche promotes glycolysis and lactate generation, resulting in the infiltration of regulatory T cell (Treg) in NSCLC. circRUNX1 acts as a miR-145 sponge, inhibiting its negative regulation of the target gene HK2, therefore facilitating glycolysis and lactate generation. The accumulation of lactic acid in the tumor microenvironment promotes Treg cell proliferation and aids immune evasion. Functionally, the suppression of circRUNX1 significantly impedes tumor development both in vitro and in vivo. These findings collectively clarity a previously unexamined mechanism linking the circRUNX1/miR-145/HK2 axis in regulation of the Warburg effect and immune evasion in NSCLC.

Keywords: Immune evasion; NSCLC; Treg cell; Warburg effect; circRUNX1.

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Conflict of interest statement

Declaration of competing interest We declare that the article we submitted on Cancer Letters 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and tacitly or explicitly by the responsible authorities where the work was carried out, and that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, including electronically without the written consent of the copyright-holder.

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