«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

29卷

期数:

2023年04期

页码:

360-365,386

栏目:

生物信息学专题

出版日期:

2023-07-10

文章信息/Info

Title:

NCOR2 expression in colon cancer and its influence on cell growth

文章编号:

1006-8147（2023）04-0360-07

作者:

冯圣鋆; 武燕洁; 宣成昊; 兰蓓

天津医科大学基础医学院生物化学与分子生物学系，天津300070

Author(s):

FENG Sheng-yun; WU Yan-jie; XUAN Cheng-hao; LAN Bei

Department of Biochemistry and Molecular Biology，School of Basic Medical Sciences，Tianjin Medical University，Tianjin 300070，China

关键词:

NCOR2; 结肠癌; 生长; 预后分析

Keywords:

NCOR2; colon cancer; growth; prognosis

分类号:

R735.3

DOI:

-

文献标志码:

A

摘要:

目的：探讨核受体辅助抑制因子2（NCOR2）在结肠癌中的表达情况及对结肠癌细胞生长的作用。方法：利用TCGA数据库分析NCOR2在结肠癌组织中的表达及与预后的关系；在细胞水平上，利用shRNA敲低结肠癌细胞系RKO和SW480细胞中NCOR2的表达，通过MTT、EdU、克隆形成及细胞凋亡实验探究敲低NCOR2对结肠癌细胞的影响；利用TCGA数据库基因表达数据，根据NCOR2的中位表达量将肿瘤组织分成NCOR2mRNA高、低表达组，筛选两组差异表达基因，进一步从高表达组下调基因中提取癌症相关的基因并分析其与NCOR2表达相关性。结果：TCGA数据分析显示，NCOR2在结肠癌组织中的表达高于正常组织（P<0.001），并且其高表达与结肠癌预后不良有关（P<0.05）；细胞水平实验证明，干扰NCOR2表达后，RKO和SW480细胞活力下降，细胞增殖能力减弱，且细胞凋亡水平增加。利用TCGA数据库发现，与低表达组相比，NCOR2高表达组共有176个上调基因，67个下调基因，并且基因相关性分析结果显示NCOR2与NRIF3（r=-0.57，P<0.001）和CHAC2（r=-0.52，P<0.001）表达呈负相关。在细胞水平上，RT-qPCR实验同样证明，NCOR2敲低后导致NRIF3和CHAC2的mRNA表达升高（tNRIF3=-15.99、tCHAC2=-10.349，均P<0.05）。结论：NCOR2在结肠癌中高表达，促进结肠癌细胞的生长，且与患者不良预后呈正相关，为结肠癌诊疗提供了新的潜在靶点。

Abstract:

Objective：To explore the expression of nuclear receptor corepressor 2 （ NCOR2） in colon cancer progression and its effect on the growth of colon cancer cells. Methods：The expression of NCOR2 in colon cancer tissues and the relationship with prognosis were analyzed using data from TCGA database. At the cellular level，shRNA was applied to knock down the expression of NCOR2 in RKO and SW480 colon cancer cell lines，and the effects of knocking down NCOR2 on colon cancer cells were examined by MTT，colony formation， EdU incorporation and Annexin V/PI staining assays. Tumor tissue was divided into NCOR2 mRNA high and low expression groups based on the median expression level of NCOR2 using gene expression data from the TCGA database. Two sets of differentially expressed genes were screened，and cancer related genes were further extracted from the down regulated genes in the high expression group and analyzed for their correlation with NCOR2 expression. Results：TCGA data analysis showed that the expression of NCOR2 was up-regulated in colon cancer tissues compared with normal tissues（ P<0.001），and the high expression of NCOR2 was related to adverse prognosis of colon cancer patients（ P<0.05）. Knockdown of NCOR2 suppressed cell viability，proliferation and enhanced apoptosis in RKO and SW480 cells. Furthermore，176 genes were upregulated and 67 genes were down regulated in NCOR2 high expression groups. Gene correlation analysis showed that NCOR2 was negatively correlated with the expression of NRIF3（ r=-0.57，P<0.001） and CHAC2（ r=-0.52，P<0.001）. At the cellular level，RT-qPCR experiments also demonstrated that knocking down NCOR2 resulted in an increase in mRNA expression of NRIF3 and CHAC2（ tNRIF3=-15.99，tCHAC2=-10.349，both P<0.05）. Conclusion：NCOR2 is highly expressed in colon cancer tissues，which promotes the growth of colon cancer cells and positively correlates with poor prognosis of patients，and provides new potential targets for the diagnosis and treatment of colon cancer.

参考文献/References:

[1] DEKKER E，TANIS P J，VLEUGELS J L A，et al. Colorectal cancer [J]. Lancet，2019，394（ 10207）：1467-1480.
[2] ARNOLD M，SIERRA M S，LAVERSANNE M，et al. Global patterns and trends in colorectal cancer incidence and mortality[J]. Gut，2017， 66（ 4）：683-691.
[3] BRAY F，FERLAY J，SOERJOMATARAM I，et al. Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin，2018， 68（ 6）：394-424.
[4] HENRIKSON N B，WEBBER E M，GODDARD K A，et al. Family history and the natural history of colorectal cancer：systematic review [J]. Genet Med，2015，17（ 9）：702-712.
[5] SIEGEL R L，MILLER K D，GODING SAUER A，et al. Colorectal cancer statistics，2020[J]. CA Cancer J Clin，2020，70（3）：145-164.
[6] NASSAR D，BLANPAIN C. Cancer stem cells：basic concepts and therapeutic implications[J]. Annu Rev Pathol，2016，11：47-76.
[7] BOAKYE D，RILLMANN B，WALTER V，et al. Impact of comorbid－ity and frailty on prognosis in colorectal cancer patients：a systematic review and meta-analysis [J]. Cancer Treat Rev，2018，64：30-39.
[8] LI J W，WANG J，WANG J X，et al. Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3 [J]. Embo J，2000，19（ 16）：4342-4350.
[9] GUENTHER M G，BARAK O，LAZAR M A. The SMRT and N-CoR corepressors are activating cofactors for histone deacetylase 3[J]. Mol Cell Biol，2001，21（ 18）：6091-6101.
[10] TSAI K K，HUANG S S，NORTHEY J J，et al. Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity [J]. Na－ture Cancer，2022，3（ 6）：734-752.
[11] LONG M D，JACOBI J J，SINGH P K，et al. Reduced NCOR2 ex－pression accelerates androgen deprivation therapy failure in prostate cancer [J]. Cell Rep，2021，37（ 11）：110109.
[12] CLEARY R K，MORRIS A M，CHANG G J，et al. Controversies in surgical oncology：does the minimally invasive approach for rectal cancer provide equivalent oncologic outcomes compared with the open approach?[J]. Ann Surg Oncol，2018，25（ 12）：3587-3595.
[13] DU D，SU Z，WANG D，et al. Optimal interval to surgery after neoad－juvant chemoradiotherapy in rectal cancer：a systematic review and meta-analysis[J]. Clin Colorectal Cancer，2018，17（ 1）：13-24.
[14] LEVIN T R，JAMIESON L，BURLEY D A，et al. Organized colorec－tal cancer screening in integrated health care systems[J]. Epidemiol Rev，2011，33（ 1）：101-110.
[15] DE WIT M，FIJNEMAN R J，VERHEUL H M，et al. Proteomics in colorectal cancer translational research：biomarker discovery for clinical applications[J]. Clin Biochem，2013，46（ 6）：466-479.
[16] MACDERMID E，HOOTON G，MACDONALD M，et al. Improving pa－tient survival with the colorectal cancer multi-disciplinary team [J]. Colorectal Dis，2009，11（ 3）：291-295.
[17] ZIELINSKA A，WLODARCZYK M，MAKARO A，et al. Management of pain in colorectal cancer patients[J]. Crit Rev Oncol Hematol，2021， 157：103122.
[18] WONG M M，GUO C，ZHANG J. Nuclear receptor corepressor com－plexes in cancer：mechanism，function and regulation[J]. Amer J Clin Exper Urol，2014，2（ 3）：169-187.
[19] LEE R D，KNUTSON T P，MUNRO S A，et al. Nuclear corepressors NCOR1/NCOR2 regulate B cell development，maintain genomic in－tegrity and prevent transformation[J]. Nat Immunol，2022，23（ 12）：1763-1776.
[20] TENG L，FENG Y C，GUO S T，et al. The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis [J]. Nat Commun，2021，12（ 1）：3734.
[21] DOBRZYCKA K M，TOWNSON S M，JIANG S，et al. Estrogen re－ceptor corepressors-a role in human breast cancer?[J]. Endocrine-related Cancer，2003，10（ 4）：517-536.
[22] TALUKDER A H，LI D Q，MANAVATHI B，et al. Serine 28 phos－phorylation of NRIF3 confers its co-activator function for estrogen receptor-alpha transactivation[J]. Oncogene，2008，27（ 39）：5233-5242.
[23] TINNIKOV A A，YEUNG K T，DAS S，et al. Identification of a novel pathway that selectively modulates apoptosis of breast cancer cells [J]. Cancer Res，2009，69（ 4）：1375-1382.
[24] LIU S，FEI W，SHI Q，et al. CHAC2，downregulated in gastric and colorectal cancers，acted as a tumor suppressor inducing apoptosis and autophagy through unfolded protein response[J]. Cell Death Dis， 2017，8（ 8）：e3009.

相似文献/References:

[1]王金淼,姜 涛,戚 峰,等.抑制microRNA-21表达降低HCT-116细胞侵袭转移能力的实验研究[J].天津医科大学学报,2016,22(01):13.
　WANG Jin-miao,JIANG Tao,QI Feng,et al.Experimental research on reducing invasion and metastasis ability of HCT-116 by inhibiting microRNA-21 expression[J].Journal of Tianjin Medical University,2016,22(04):13.
[2]张婷婷,张广华.右美托咪定持续输注对结肠癌手术麻醉的影响[J].天津医科大学学报,2017,23(01):62.
[3]王多伟,Bikash Rai,王金淼,等.Twist基因对结肠癌细胞系侵袭转移能力影响的体外研究[J].天津医科大学学报,2017,23(06):510.
　WANG Duo-wei,Bikash Rai,WANG Jin-miao,et al.Research on the influence of Twist gene on invasion and metastasis of colon cancer cell lines in vitro[J].Journal of Tianjin Medical University,2017,23(04):510.
[4]刘惠芳,邓靖宇 综述,梁 寒 审校.KLHL6在肿瘤研究中的进展[J].天津医科大学学报,2017,23(06):569.
[5]马博昭,王小东,王金淼,等.吡非尼酮抑制肿瘤相关成纤维细胞促进结肠癌细胞系HT29上皮间质转化的作用及机制[J].天津医科大学学报,2018,24(05):399.
　MA Bo-zhao,WANG Xiao-dong,WANG Jin-miao,et al.Effect and mechanism of pirfenidone on epithelial-mesenchymal transition induced by cancer-associated fibroblasts in HT29 colon cancer cell lines[J].Journal of Tianjin Medical University,2018,24(04):399.
[6]王小东,马博昭,戚 峰.MiR-148a-3p通过靶向SRPK2抑制结肠癌细胞转移[J].天津医科大学学报,2019,25(02):99.
　WANG Xiao-dong,MA Bo-zhao,QI Feng.MiR-148a-3p inhibits colon cancer cell metastasis by targeting SRPK2[J].Journal of Tianjin Medical University,2019,25(04):99.
[7]潘琼,谷见法,刘松格,等.miR-133过表达对结肠癌细胞SW480凋亡、增殖和裸鼠成瘤的影响[J].天津医科大学学报,2021,27(05):472.
　PAN Qiong,GU Jian-fa,LIU Song-Ge,et al.Effects of miR-133 overexpression on apoptosis，proliferation and tumor formation of colon cancer cells SW480 in nude mice[J].Journal of Tianjin Medical University,2021,27(04):472.
[8]张倩倩,时涵远,李馨航,等.甘油三酯-葡萄糖指数和血浆致动脉硬化指数评价冠心病的临床价值[J].天津医科大学学报,2022,28(01):73.
　ZHANG Qian-qian,SHI Han-yuan,LI Xin-hang,et al.Clinical significance of triglyceride-glucose index and atherogenic index of plasma in evaluating coronary heart disease[J].Journal of Tianjin Medical University,2022,28(04):73.
[9]管君,荀敬,王波涛,等.薯蓣皂苷对人结肠癌细胞凋亡的作用及机制研究[J].天津医科大学学报,2022,28(05):483.
　GUAN Jun,XUN Jing,WANG Bo-tao,et al.The effect and underlying mechanism of Dioscin on apoptosis of human colon cancer cells[J].Journal of Tianjin Medical University,2022,28(04):483.

备注/Memo

备注/Memo:

作者简介冯圣鋆（1996-），男，硕士在读，研究方向：肿瘤表观遗传学；
通信作者：宣成昊，E-mail：chenghaoxuan@tmu.edu.cn；兰蓓， E-mail：lanpei@tmu.edu.cn。

常用功能

更新日期/Last Update: 2023-07-10