title: XRCC2 promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis.
abstract: X-ray repair complementing defective repair in Chinese hamster cells 2 (XRCC2) and poly(ADP-ribose) polymerase 1 (PARP1) both play important roles in homologous recombination DNA repair. According to the theory of synthetic lethality, XRCC2-deficient cells are more sensitive to PARP1 inhibitors compared to XRCC2-expressing cells. We investigated XRCC2 expression and function in colorectal cancer (CRC), and the characteristics of sensitivity to PARP1 inhibitor in CRC cells with different XRCC2 levels. We enrolled 153 patients with CRC who had undergone surgery in this study. XRCC2 expression was assessed using immunohistochemistry. Stable CRC SW480 cell lines with low or high XRCC2 expression were constructed. Following treatment with the PARP1 inhibitor olaparib, the viability of cells with different XRCC2 levels was determined; cell cycle distribution and apoptosis were analyzed using flow cytometry. B-cell lymphoma-2 (Bcl-2) protein expression was measured by Western blotting. The positive rates of XRCC2 in primary CRC tissue were significantly higher than that in the matched adjacent noncancerous tissue, and XRCC2 expression status in primary CRC was related to tumor site, Dukes' stage, and tumor-nodes-metastasis (TNM) stage. XRCC2 overexpression inhibited CRC cell apoptosis and promoted proliferation by enriching cells in the G0/G1 phase. Moreover, olaparib suppressed proliferation, and olaparib sensitivity in CRC cells with high XRCC2 expression was greater. High XRCC2 expression promotes CRC cell proliferation and enriches cells in the G0/G1 phase but inhibits apoptosis. High XRCC2 expression cells are more sensitive to olaparib, which inhibits their viability.
authors.affiliation: From the Gastrointestinal and Pancreatic Surgery Department, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Kaiwu
authors.initials: K
authors.lastname: Xu
authors.forename: Xinming
authors.initials: X
authors.lastname: Song
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Chen
authors.forename: Changjiang
authors.initials: C
authors.lastname: Qin
authors.forename: Yulong
authors.initials: Y
authors.lastname: He
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhan
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics*; D048708:Cell Growth Processes / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
chemical_list: D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; C113187:XRCC2 protein, human