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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.

SUBMITTER: Xu K

PROVIDER: S-EPMC4603138 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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XRCC2 promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis.

Xu Kaiwu K Song Xinming X Chen Zhihui Z Qin Changjiang C He Yulong Y Zhan Wenhua W

Medicine 20141201 28

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 le ...[more]

PMID: 25526472

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Project description:Objective: To elucidate how lncRNA 00668 (LINC00668) influences the development of breast cancer (BC). Materials and methods: Genome-wide expression profile of BC and paracancerous tissues were downloaded from The Cancer Genome Atlas (TCGA) and BC tissues and paracancerous tissues enrolled from our hospital for analyzing the expression level of LINC00668 and its correlation with prognosis. GSEA was conducted to analyze the potential functions of LINC00668. By transfection of sh-LINC00668 in BC cells, proliferation, apoptosis, cell cycle and colony formation of BC cells were accessed. Western blot was conducted to detect protein expressions of Ki-67, CDK4, Bcl-2, p21 and genes in AKT/mTOR pathways after LINC00668 knockdown in BC cells. Finally, tumor-bearing nude mice were administrated with BC cells. We compared the proliferative rate in mice with different administrations. Immunohistochemistry was carried out to access expression levels of Ki-67, CDK4, Bcl-2 and P21 in mice. Results: Both TCGA data and BC tissues harvested from our hospital indicated the higher expression of LINC00668 in BC tissues. LINC00668 expression was negatively correlated to prognosis of BC patients. GSEA pointed out that LINC00668 is enriched in regulations of cell cycle and apoptosis. By transfection of sh-LINC00668 in MDA-MB-231 and MDA-MB-436 cells, the proliferative and colony formation abilities of BC cells decreased. Besides, LINC00668 knockdown in BC cells induced apoptosis and arrested cell cycle. LINC00668 knockdown downregulated Ki-67, CDK4 and Bcl-2, but upregulated p21. The AKT/mTOR pathway was inhibited after LINC00668 silenced. In vivo experiments demonstrated the decreased proliferative rate in tumor-bearing mice administrated with sh-LINC00668 transfected BC cells. Consistently, immunohistochemical results showed lower positive expressions of Ki-67, CDK4 and Bcl-2, but higher positive expression of p21 in sh-LINC00668 group. Conclusion: LINC00668 is highly expressed in BC tissues and can promote the progression of BC by inhibiting apoptosis and accelerating cell cycle progression.

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XRCC2 promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis.

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XRCC2 promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis.

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