EHMT2‐mediated R‐loop formation promotes the malignant progression of prostate cancer via activating Aurora B DOI Creative Commons
Yuyang Zhang,

Mingqin Su,

Yi‐Ming Chen

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background Chromosomal instability (CIN), a hallmark of cancer, is commonly linked to poor prognosis in high‐grade prostate cancer (PCa). Paradoxically, excessively high levels CIN may impair cell viability. Consequently, understanding how tumours adapt critical for identifying novel therapeutic targets. Methods Bioinformatic analyses were conducted identify genes overexpressed PCa tissues using The Cancer Genome Atlas (TCGA) and GEO datasets. Western blotting immunohistochemistry assays applied determine the expression euchromatic histone lysine methyltransferase 2 (EHMT2), pT232‐Aurora B Cullin 3 (CUL3). proliferation cells was measured through CCK‐8 tests, clonogenesis subcutaneous xenografts human BALB/c nude mice. Live imaging, immunofluorescence (IF) flow cytometry used confirm role EHMT2 mitosis. Co‐immunoprecipitation, IF further elucidated underlying molecular mechanisms. Results highly expressed metastatic exhibiting elevated strongly associated with adverse clinical outcomes patients PCa. Silencing impaired division, inducing G2/M‐phase arrest mitotic catastrophe cells. Mechanistically, indispensable ensure full activation Aurora centromeric R‐loop‐driven ATR–CHK1 pathway, protein peaking during G2/M‐phase. Moreover, CUL3 identified as binding partner EHMT2, mediating its polyubiquitination destabilising levels. Conclusions This study reveals CUL3–EHMT2–Aurora regulatory axis that safeguards accurate chromosome segregation cells, supporting potential application inhibitors. Key points Euchromatic (EHMT2) advanced restraining catastrophic chromosomal (CIN) enhancing fitness. functions via ATR–CHK1–Aurora pathway promote stability. confers enzalutamide resistance activating B. (CUL3) promotes destabilisation deubiquitination.

Language: Английский

EHMT2‐mediated R‐loop formation promotes the malignant progression of prostate cancer via activating Aurora B DOI Creative Commons
Yuyang Zhang,

Mingqin Su,

Yi‐Ming Chen

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Abstract Background Chromosomal instability (CIN), a hallmark of cancer, is commonly linked to poor prognosis in high‐grade prostate cancer (PCa). Paradoxically, excessively high levels CIN may impair cell viability. Consequently, understanding how tumours adapt critical for identifying novel therapeutic targets. Methods Bioinformatic analyses were conducted identify genes overexpressed PCa tissues using The Cancer Genome Atlas (TCGA) and GEO datasets. Western blotting immunohistochemistry assays applied determine the expression euchromatic histone lysine methyltransferase 2 (EHMT2), pT232‐Aurora B Cullin 3 (CUL3). proliferation cells was measured through CCK‐8 tests, clonogenesis subcutaneous xenografts human BALB/c nude mice. Live imaging, immunofluorescence (IF) flow cytometry used confirm role EHMT2 mitosis. Co‐immunoprecipitation, IF further elucidated underlying molecular mechanisms. Results highly expressed metastatic exhibiting elevated strongly associated with adverse clinical outcomes patients PCa. Silencing impaired division, inducing G2/M‐phase arrest mitotic catastrophe cells. Mechanistically, indispensable ensure full activation Aurora centromeric R‐loop‐driven ATR–CHK1 pathway, protein peaking during G2/M‐phase. Moreover, CUL3 identified as binding partner EHMT2, mediating its polyubiquitination destabilising levels. Conclusions This study reveals CUL3–EHMT2–Aurora regulatory axis that safeguards accurate chromosome segregation cells, supporting potential application inhibitors. Key points Euchromatic (EHMT2) advanced restraining catastrophic chromosomal (CIN) enhancing fitness. functions via ATR–CHK1–Aurora pathway promote stability. confers enzalutamide resistance activating B. (CUL3) promotes destabilisation deubiquitination.

Language: Английский

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