Nucleolar protein treacle ribosome biogenesis factor 1 maintains gastric cancer cell proliferation by regulating R‐loop associated DNA replication stress

• DOI: 10.1111/jgh.16181
• Publication Date: 2023-03-21T02:09:50Z
• Authors: Xin Nie; Chong Zhao; Yuan Zhang; Wenqi Huang; Youlian Zhou; Haiying Liu; Yuqiang Nie; Keping Xie; Lin Jia
• Keywords: ribosome biogenesis

Abstract Background and Aim Gastric cancer (GC) is a common malignant neoplasm in the gastrointestinal tract, accounting for high mortality globally. Treacle ribosome biogenesis factor 1 (TCOF1) nucleolar protein, which has been reported to be implicated pathogenesis of Treacher Collins syndrome development several types human cancer. However, role TCOF1 GC not known. Methods Immunohistochemistry was carried out determine expression tissues. Immunofluorescence, co‐IP, DNA fiber assays were conducted investigate function GC‐derived BGC‐823 SGC‐7901 cell lines. Results aberrantly increased tissues compared with adjacent normal In addition, we found that left nucleolus localized R‐loops (DNA/RNA hybrids) during S phase cells. Furthermore, interacted DDX5 suppressed R‐loop levels. Knockdown led nucleoplasmic specifically phase, restrained replication proliferation. Overexpression eraser RNaseH1 rescued synthesis defects decreased damage caused by depletion. Conclusion These findings demonstrate novel maintaining proliferation alleviating associated stress.