Qkiinduced Circ0001766 Inhibits Colorectal Cancer Progression And Rapamycin Resistance By Mir1203ppp1r3cmtormyc Axis Yulai Zhou Yan Gao Yinghui Peng Changjing Cai Ying Han Yihong Chen Gongping Deng Yanhong Ouyang Hong Shen Shan Zeng Yangfeng Du Zemin Xiao by Yulai Zhou & Yan Gao & Yinghui Peng & Changjing Cai & Ying Han & Yihong Chen & Gongping Deng & Yanhong Ouyang & Hong Shen & Shan Zeng & Yangfeng Du & Zemin Xiao instant download after payment.

Colorectal cancer (CRC) is the third most common cancer and remains a significant challenge due to high rates of drug resistanceand limited therapeutic options. Circular RNAs (circRNAs) are increasingly recognized for their roles in CRC initiation, progression,and drug resistance. However, no circRNA-based therapies have yet entered clinical development, underscoring the need forcomprehensive detection and mechanistic studies of circRNAs in CRC. Here, we identified and characterized a circular RNA,circ_0001766 (hsa_circ_0001766), through microarray analysis of CRC tissues. Our results showed that circ_0001766 is1234567890();,:downregulated in CRC tissues and closely associated with patient survival and metastasis. Functional experiments demonstratedthat circ_0001766 inhibits CRC cell proliferation, migration and invasion both in-vitro and in-vivo. Mechanistically, hypoxiadownregulates Quaking (QKI), an RNA-binding protein essential for the biogenesis of circ_0001766 by binding to introns 1 and 3 ofPDIA4 pre-mRNA. Reduced QKI expression under hypoxic conditions leads to decreased circ_0001766 levels in CRC. Circ_0001766acts as a competitive endogenous RNA, sponging miR-1203 to prevent the degradation of PPP1R3C mRNA. Loss of circ_0001766results in decreased PPP1R3C expression, leading to the activation of mTOR signaling and increased phosphorylation of Myc, whichpromotes CRC progression and rapamycin resistance. Our study reveals that overexpression of circ_0001766 or PPP1R3C in CRC cellsinhibits the mTOR and Myc pathway, thereby resensitizing cells to rapamycin. The combination of circ_0001766 or PPP1R3C withrapamycin markedly inhibits CRC cell proliferation and induces apoptosis by reducing rapamycin-induced Myc phosphorylation. Insummary, our study elucidates a critical circ_0001766/miR-1203/PPP1R3C axis that modulates CRC progression and rapamycinresistance. Our findings highlight circ_0001766 as a promising therapeutic target in CRC, providing a new avenue for enhancing theefficacy of existing treatments and overcoming drug resistance.Cell Death Discovery (2025) 11:192 ;