转录因子ZBTB18对结直肠癌细胞转移的影响
|
摘要
目的观察转录因子ZBTB18对结直肠癌细胞的生长的影响。方法从NCBI GEO数据库中下载肿瘤基因表达芯片数据,对ZBTB18基因的表达水平进行分析;同时通过RNA干扰和Transwell实验研究ZBTB18对结直肠癌细胞迁移的影响。结果 ZBTB18蛋白表达于结直肠癌细胞系,且高转移能力的细胞系中该蛋白的表达水平远高于原发性结直肠癌肿瘤细胞系(P<0. 05)。RNA干扰试验可特异性地显著沉默结直肠癌细胞HT29中ZBTB18的表达,Transwell实验发现在ZBTB18沉默后HT29细胞的侵袭和迁移能力显著降低(P<0. 05)。结论转录因子ZBTB18可以促进结直肠癌细胞的侵袭与迁移,可能参与结直肠癌的转移。
Objective To study the effect of ZBTB18 on the colorectal cancer cell growth.Methods The expression profiling data of colorectal cancer was downloaded from the public database NCBI GEO and the expression of ZBTB18 was analyzed specifically. We detected ZBTB18 expression levels by quantitative PCR in multiple colorectal cancer cell lines,reduced its expression level by RNAi and observed the cell invasion and migration by Transwell experiment. Results The expression level of ZBTB18 in metastatic tumor cells was higher than that in non-metastatic tumor cells( P<0. 05). After reducing the expression of ZBTB18 in HT29 cells by RNAi,we found the down expression of ZBTB18 could significantly inhibit the cell invasion and migration in vitro( P <0. 05). Conclusion Transcription factor ZBTB18 could promote the invasion and migration of colorectal cancer cells,suggesting that ZBTB18 may promote colorectal cancer metastasis.
Objective To study the effect of ZBTB18 on the colorectal cancer cell growth.Methods The expression profiling data of colorectal cancer was downloaded from the public database NCBI GEO and the expression of ZBTB18 was analyzed specifically. We detected ZBTB18 expression levels by quantitative PCR in multiple colorectal cancer cell lines,reduced its expression level by RNAi and observed the cell invasion and migration by Transwell experiment. Results The expression level of ZBTB18 in metastatic tumor cells was higher than that in non-metastatic tumor cells( P<0. 05). After reducing the expression of ZBTB18 in HT29 cells by RNAi,we found the down expression of ZBTB18 could significantly inhibit the cell invasion and migration in vitro( P <0. 05). Conclusion Transcription factor ZBTB18 could promote the invasion and migration of colorectal cancer cells,suggesting that ZBTB18 may promote colorectal cancer metastasis.
引文
[1]Theodoratou E,Timofeeva M,Li X,et al.Nature,nurture,and cancer risks:genetic and nutritional contributions to cancer[J].Annu Rev Nutr,2017,37:293-320.
[2]US Preventive Services Task Force,Bibbins-Domingo K,Grossman DC,et al.Screening for colorectal cancer:USpreventive services task force recommendation statement[J].JAMA,2016,315(23):2564-2575.
[3]Zheng Shu,Cai Shanrong.Colorectal cancer epidemiology and prevention study in China[J].The Chinese-German Journal of Clinical Oncology,2003,2(2):72-75.
[4]周伦,余海,郑树.结直肠癌优化筛检方案在大肠癌高发区人群中的验证[J].中国慢性病预防与控制,1997,5(2):75-76.
[5]Stangl R,Altendorf-Hofmann A,Charnley RM,et al.Factors influencing the natural history of colorectal liver metastases[J].Lancet,1994,343(8910):1405-1410.
[6]Ehmke N,Karge S,Buchmann J,et al.A de novo nonsense mutation in ZBTB18 plus a de novo 15q13.3 microdeletion in a 6-year-old female[J].Am J Med Genet A,2017,173(5):1251-1256.
[7]Depienne C,Nava C,Keren B,et al.Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU[J].Hum Genet,2017,136(4):463-479.
[8]Cohen JS,Srivastava S,Farwell Hagman KD,et al.Further evidence that de novo missense and truncating variants in ZBTB18 cause intellectual disability with variable features[J].Clin Genet,2017,91(5):697-707.
[9]Fedele V,Dai F,Masilamani AP,et al.Epigenetic regulation of ZBTB18 promotes glioblastoma progression[J].Mol Cancer Res,2017,15(8):998-1011.
[10]Tatard VM,Xiang C,Biegel JA,et al.ZNF238 is expressed in postmitotic brain cells and inhibits brain tumor growth[J].Cancer Res,2010,70(3):1236-1246.
[11]Brouwer-Visser J,Cheng WY,Bauer-Mehren A,et al.Regulatory T-cell genes drive altered immune microenvironment in adult solid cancers and allow for immune contextual patient subtyping[J].Cancer Epidemiol Biomarkers Prev,2018,27(1):103-112.
[12]Liotta LA,Stetler-Stevenson WG.Tumor invasion and metastasis:an imbalance of positive and negative regulation[J].Cancer Res,1991,51(18 Suppl):5054s-5059s.
[13]Sobel ME.Metastasis suppressor genes[J].J Natl Cancer Inst,1990,82(4):267-276.
[14]Mannava S,Grachtchouk V,Wheeler LJ,et al.Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells[J].Cell cycle,7(15):2392-2400.
[15]Hartman DJ,Davison JM,Foxwell TJ,et al.Mutant allelespecific imbalance modulates prognostic impact of KRASmutations in colorectal adenocarcinoma and is associated with worse overall survival[J].Int J Cancer,2012,131(8):1810-1817.
[16]Dizdar L,Werner TA,Drusenheimer JC,et al.BRAF(V600E)mutation:a promising target in colorectal neuroendocrine carcinoma[J].Int J Cancer,2019,144(6):1379-1390.
[17]Delfino FJ,Stevenson H,Smithgall TE.A growth-suppressive function for the c-fes protein-tyrosine kinase in colorectal cancer[J].T J Biol Chem,2006,281(13):8829-8835.
[18]Webb MW,Sun J,Sheard MA,et al.Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of Tlymphocytes[J].Int J Cancer,2018,143(6):1483-1493.
[19]Maroni P,Matteucci E,Bendinelli P,et al.Functions and epigenetic regulation of wwox in bone metastasis from breast carcinoma:comparison with primary tumors[J].Int J Mol Sci,2017,18(1):E75.
[20]Kumar A,Hatwal D,Batra N,et al.Role of nm23H1 in predicting metastases in prostatic carcinoma[J].Indian JPathol Microbiol,2018,61(1):70-75.
[21]Shen SM,Ji Y,Zhang C,et al.Nuclear PTEN safeguards pre-m RNA splicing to link Golgi apparatus for its tumor suppressive role[J].Nat Commun,2018,9(1):2392.
[22]Aaberg-Jessen C,Sorensen MD,Matos A,et al.Co-expression of TIMP-1 and its cell surface binding partner CD63in glioblastomas[J].BMC cancer,2018,18(1):270.
[23]Okado H.Regulation of brain development and brain function by the transcriptional repressor RP58[J].Brain Res,2018,1705:15-23.
[2]US Preventive Services Task Force,Bibbins-Domingo K,Grossman DC,et al.Screening for colorectal cancer:USpreventive services task force recommendation statement[J].JAMA,2016,315(23):2564-2575.
[3]Zheng Shu,Cai Shanrong.Colorectal cancer epidemiology and prevention study in China[J].The Chinese-German Journal of Clinical Oncology,2003,2(2):72-75.
[4]周伦,余海,郑树.结直肠癌优化筛检方案在大肠癌高发区人群中的验证[J].中国慢性病预防与控制,1997,5(2):75-76.
[5]Stangl R,Altendorf-Hofmann A,Charnley RM,et al.Factors influencing the natural history of colorectal liver metastases[J].Lancet,1994,343(8910):1405-1410.
[6]Ehmke N,Karge S,Buchmann J,et al.A de novo nonsense mutation in ZBTB18 plus a de novo 15q13.3 microdeletion in a 6-year-old female[J].Am J Med Genet A,2017,173(5):1251-1256.
[7]Depienne C,Nava C,Keren B,et al.Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU[J].Hum Genet,2017,136(4):463-479.
[8]Cohen JS,Srivastava S,Farwell Hagman KD,et al.Further evidence that de novo missense and truncating variants in ZBTB18 cause intellectual disability with variable features[J].Clin Genet,2017,91(5):697-707.
[9]Fedele V,Dai F,Masilamani AP,et al.Epigenetic regulation of ZBTB18 promotes glioblastoma progression[J].Mol Cancer Res,2017,15(8):998-1011.
[10]Tatard VM,Xiang C,Biegel JA,et al.ZNF238 is expressed in postmitotic brain cells and inhibits brain tumor growth[J].Cancer Res,2010,70(3):1236-1246.
[11]Brouwer-Visser J,Cheng WY,Bauer-Mehren A,et al.Regulatory T-cell genes drive altered immune microenvironment in adult solid cancers and allow for immune contextual patient subtyping[J].Cancer Epidemiol Biomarkers Prev,2018,27(1):103-112.
[12]Liotta LA,Stetler-Stevenson WG.Tumor invasion and metastasis:an imbalance of positive and negative regulation[J].Cancer Res,1991,51(18 Suppl):5054s-5059s.
[13]Sobel ME.Metastasis suppressor genes[J].J Natl Cancer Inst,1990,82(4):267-276.
[14]Mannava S,Grachtchouk V,Wheeler LJ,et al.Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells[J].Cell cycle,7(15):2392-2400.
[15]Hartman DJ,Davison JM,Foxwell TJ,et al.Mutant allelespecific imbalance modulates prognostic impact of KRASmutations in colorectal adenocarcinoma and is associated with worse overall survival[J].Int J Cancer,2012,131(8):1810-1817.
[16]Dizdar L,Werner TA,Drusenheimer JC,et al.BRAF(V600E)mutation:a promising target in colorectal neuroendocrine carcinoma[J].Int J Cancer,2019,144(6):1379-1390.
[17]Delfino FJ,Stevenson H,Smithgall TE.A growth-suppressive function for the c-fes protein-tyrosine kinase in colorectal cancer[J].T J Biol Chem,2006,281(13):8829-8835.
[18]Webb MW,Sun J,Sheard MA,et al.Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of Tlymphocytes[J].Int J Cancer,2018,143(6):1483-1493.
[19]Maroni P,Matteucci E,Bendinelli P,et al.Functions and epigenetic regulation of wwox in bone metastasis from breast carcinoma:comparison with primary tumors[J].Int J Mol Sci,2017,18(1):E75.
[20]Kumar A,Hatwal D,Batra N,et al.Role of nm23H1 in predicting metastases in prostatic carcinoma[J].Indian JPathol Microbiol,2018,61(1):70-75.
[21]Shen SM,Ji Y,Zhang C,et al.Nuclear PTEN safeguards pre-m RNA splicing to link Golgi apparatus for its tumor suppressive role[J].Nat Commun,2018,9(1):2392.
[22]Aaberg-Jessen C,Sorensen MD,Matos A,et al.Co-expression of TIMP-1 and its cell surface binding partner CD63in glioblastomas[J].BMC cancer,2018,18(1):270.
[23]Okado H.Regulation of brain development and brain function by the transcriptional repressor RP58[J].Brain Res,2018,1705:15-23.