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<p>RecQ-mediated genome instability protein 2 (RMI2), a component of the RecQ helicase complex, has been shown to be highly expressed in various cancers and is often associated with poorer patient survival. However, its specific role in ovarian cancer (OC) remains unclear. This study investigates whether RMI2 contributes to OC progression via the ATR/CHK1 pathway. Bioinformatics analysis and experimental validation revealed that RMI2 was highly expressed in OC tissues and cell lines compared with normal controls. Functional assays demonstrated that knockdown of RMI2 inhibited OC cell proliferation and colony formation, induced G<sub>2</sub>/M phase arrest, and promoted apoptosis. Furthermore, the knockdown of RMI2 led to increased DNA damage (manifested as the accumulation of γH2AX) and downregulated homologous recombination repair proteins (BRCA1, NBS1, RAD51). Under DNA damage stress induced by Olaparib, a Poly (ADP-ribose) Polymerase (PARP) inhibitor, RMI2 knockdown synergistically enhanced DNA damage and apoptosis. Mechanistically, RMI2 directly interacted with ATR, and its knockdown reduced ATR phosphorylation and the expression of its downstream effector CHK1. Additionally, overexpression of ATR partially rescued the inhibitory effects of RMI2 knockdown on OC cell growth and DNA damage. In conclusion, RMI2 may promote OC development by activating the ATR/CHK1 pathway to sustain genomic stability, highlighting its potential as a prognostic biomarker and therapeutic target in OC.</p>

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RMI2 knockdown suppresses ovarian cancer cell growth by impairing DNA damage repair via the ATR/CHK1 signaling pathway

  • 期刊论文

  • 发表日期：

    2026年7月10日

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  • Kean Zhu,
  • Zhao Li,
  • Yingying Wei,
  • Ying Lin

摘要

RecQ-mediated genome instability protein 2 (RMI2), a component of the RecQ helicase complex, has been shown to be highly expressed in various cancers and is often associated with poorer patient survival. However, its specific role in ovarian cancer (OC) remains unclear. This study investigates whether RMI2 contributes to OC progression via the ATR/CHK1 pathway. Bioinformatics analysis and experimental validation revealed that RMI2 was highly expressed in OC tissues and cell lines compared with normal controls. Functional assays demonstrated that knockdown of RMI2 inhibited OC cell proliferation and colony formation, induced G2/M phase arrest, and promoted apoptosis. Furthermore, the knockdown of RMI2 led to increased DNA damage (manifested as the accumulation of γH2AX) and downregulated homologous recombination repair proteins (BRCA1, NBS1, RAD51). Under DNA damage stress induced by Olaparib, a Poly (ADP-ribose) Polymerase (PARP) inhibitor, RMI2 knockdown synergistically enhanced DNA damage and apoptosis. Mechanistically, RMI2 directly interacted with ATR, and its knockdown reduced ATR phosphorylation and the expression of its downstream effector CHK1. Additionally, overexpression of ATR partially rescued the inhibitory effects of RMI2 knockdown on OC cell growth and DNA damage. In conclusion, RMI2 may promote OC development by activating the ATR/CHK1 pathway to sustain genomic stability, highlighting its potential as a prognostic biomarker and therapeutic target in OC.