COL12A1在胃癌中的表达及其生物学功能研究
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摘要
目的:探讨COL12A1在胃癌中的表达水平和生物学功能。方法:利用Oncomine与GEPIA在线数据库分析COL12A1在胃癌中的表达及其与胃癌病理分期和预后的关系;用qPCR和免疫组化检测COL12A1基因与蛋白在58例胃癌及癌旁组织中的表达;用siRNA干扰技术敲低胃癌细胞SGC7901中COL12A1的表达后,通过CCK-8、平板克隆存活及Transwell小室实验分析SGC7901生物学行为的变化。结果:Oncomine与GEPIA在线数据库分析结果显示,COL12A1在胃癌中的表达水平明显升高(均P<0.05);COL12A1表达与胃癌病理分期无明显关系(P>0.05),但COL12A1高表达胃癌患者总体生存率明显降低(P<0.05)。qPCR和免疫组化结果显示,胃癌组织中COL12A1基因与蛋白表达均明显高于其癌旁组织(均P<0.05)。敲低COL12A1后,SGC7901的生长、增殖和侵袭能力明显降低(均P<0.05)。结论:COL12A1在胃癌中高表达,其高表达可能促进胃癌细胞生长、增殖和侵袭,并与患者不良预后密切相关。
Objective: To investigate the expression of COL12 A1 in gastric cancer and its biological function. Methods: Th e COL12 A1 expression in gastric cancer and its relations with pathological stage and prognosis of gastric cancer were analyzed by using Oncomine and GEPIA online databases. Th e gene and protein expressions of CLL12 A1 in 58 specimens of gastric cancer and tumor adjacent tissue were determined by qPCR and immunohistochemical staining. In gastric cancer SGC7901 cells after CLL12 A1 knockdown through siRNA interference technique, the changes in biological behaviors were observed through CCK-8 assay, plate clone formation assay, and Transwell chamber assay, respectively.Results: Oncomine-and GEPIA-based online analysis indicated that COL12 A1 was significantly upregulated in gastric cancer(both P<0.05); COL12 A1 expression was irrelevant to the pathological stage of gastric cancer(P>0.05), but the overall survival rate in gastric cancer patients with high COL12 A1 expression was signifi cantly decreased(P<0.05). the results of qPCR and immunohistochemical staining showed that both gene and protein expressions of COL12 A1 were significantly higher than those in the tumor adjacent tissue(both P<0.05). In gastric cancer SGC7901 cells aft er CLL12 A1 knockdown, the growth, proliferative and invasion abilities were all signifi cantly inhibited(all P<0.05).Conclusion: COL12 A1 is upregulated in gastric cancer, and high COL12 A1 expression may probably promote growth, proliferative and invasion abilities of gastric cancer cells, and also related to poor prognosis of the patients.
Objective: To investigate the expression of COL12 A1 in gastric cancer and its biological function. Methods: Th e COL12 A1 expression in gastric cancer and its relations with pathological stage and prognosis of gastric cancer were analyzed by using Oncomine and GEPIA online databases. Th e gene and protein expressions of CLL12 A1 in 58 specimens of gastric cancer and tumor adjacent tissue were determined by qPCR and immunohistochemical staining. In gastric cancer SGC7901 cells after CLL12 A1 knockdown through siRNA interference technique, the changes in biological behaviors were observed through CCK-8 assay, plate clone formation assay, and Transwell chamber assay, respectively.Results: Oncomine-and GEPIA-based online analysis indicated that COL12 A1 was significantly upregulated in gastric cancer(both P<0.05); COL12 A1 expression was irrelevant to the pathological stage of gastric cancer(P>0.05), but the overall survival rate in gastric cancer patients with high COL12 A1 expression was signifi cantly decreased(P<0.05). the results of qPCR and immunohistochemical staining showed that both gene and protein expressions of COL12 A1 were significantly higher than those in the tumor adjacent tissue(both P<0.05). In gastric cancer SGC7901 cells aft er CLL12 A1 knockdown, the growth, proliferative and invasion abilities were all signifi cantly inhibited(all P<0.05).Conclusion: COL12 A1 is upregulated in gastric cancer, and high COL12 A1 expression may probably promote growth, proliferative and invasion abilities of gastric cancer cells, and also related to poor prognosis of the patients.
引文
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[18]Lei H,Gao Y,Xu X.LncRNA TUG1 infl uences papillary thyroid cancer cell proliferation,migration and EMT formation through targeting miR-145[J].Acta Biochim Biophys Sin(Shanghai),2017,49(7):588-597.doi:10.1093/abbs/gmx047.
[19]吴至佛,姚晓艺,汪灵,等.紫杉醇诱导三阴性乳腺癌细胞自噬相关蛋白LC3的表达及其作用[J].中国普通外科杂志,2018,27(6):732-739.doi:10.3978/j.issn.1005-6947.2018.06.012.Wu ZF,Yao XY,Wang L,et al.Paclitaxel induced expression of autophagy-associated protein LC3 in triple negative breast cancer cells and its action[J].Chinese Journal of General Surgery,2018,27(6):732-739.doi:10.3978/j.issn.1005-6947.2018.06.012.
[20]Cui J,Chen Y,Chou WC,et al.An integrated transcriptomic and computational analysis for biomarker identification in gastric cancer[J].Nucleic Acids Res,2011,39(4):1197-1207.doi:10.1093/nar/gkq960.
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[22]Song Z,Wu Y,Yang J,et al.Progress in the treatment of advanced gastric cancer[J].Tumour Biol,2017,39(7):1010428317714626.doi:10.1177/1010428317714626.
[23]Zhuo C,Li X,Zhuang H,et al.Elevated THBS2,COL1A2,and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis[J].Cell Physiol Biochem,2016,40(6):1316-1324.doi:10.1159/000453184.
[24]Lee KS,Park GS,Hong SH,et al.Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma[J].Tumour Biol,2010,31(3):165-170.doi:10.1007/s13277-010-0022-z.
[25]Dabiri A,Baghaei K,Hashemi M,et al.Identification of differentially-expressed of Olfactomedin-related proteins 4 and COL11A1 in Iranian patients with intestinal gastric cancer[J].Gastroenterol Hepatol Bed Bench,2017,10(Suppl1):S62-69.
[26]Ruan HL,Hong RT,Xie HJ,et al.Signifi cance of elevated levels of collagen type IV and hyaluronic acid in gastric juice and serum in gastric cancer and precancerous lesion[J].Dig Dis Sci,2011,56(7):2001-2008.doi:10.1007/s10620-011-1571-8.
[27]Malik R,Lelkes PI,Cukierman E.Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer[J].Trends Biotechnol,2015,33(4):230-236.doi:10.1016/j.tibtech.2015.01.004.
[28]Sangaletti S,Chiodoni C,Tripodo C,et al.The good and bad of targeting cancer-associated extracellular matrix[J].Curr Opin Pharmacol,2017,35:75-82.doi:10.1016/j.coph.2017.06.003.
[29]Jang M,Koh I,Lee JE,et al.Increased extracellular matrix density disrupts E-cadherin/β-catenin complex in gastric cancer cells[J].Biomater Sci,2018,6(10):2704-2713.doi:10.1039/c8bm00843d.
[2]Figueiredo C,Camargo M C,Leite M,et al.Pathogenesis of Gastric Cancer:Genetics and Molecular Classifi cation[J].Curr Top Microbiol Immunol,2017,400:277-304.doi:10.1007/978-3-319-50520-6_12.
[3]肖磊,黄昌浩,袁伟杰,等.胃癌组织YAP1、E-cadherin、N-cadherin表达及临床意义[J].中国普通外科杂志,2018,27(4):442-448.doi:10.3978/j.issn.1005-6947.2018.04.009.Xiao L,Huang CH,Yuan WJ,et al.Expressions of YAP1,E-cadherin and N-cadherin in gastric cancer tissue and their clinical signifi cance[J].Chinese Journal of General Surgery,2018,27(4):442-448.doi:10.3978/j.issn.1005-6947.2018.04.009.
[4]左婷婷,郑荣寿,曾红梅,等.中国胃癌流行病学现状[J].中国肿瘤临床,2017,44(1):52-58.doi:10.3969/j.issn.1000-8179.2017.01.881.Zuo TT,Zheng RS,Zeng HM,et al.Epidemiology of stomach cancer in China[J].Chinese Journal of Clinical Oncology,2017,44(1):52-58.doi:10.3969/j.issn.1000-8179.2017.01.881.
[5]Oudart JB,Monboisse JC,Maquart FX,et al.Type XIX collagen:A new partner in the interactions between tumor cells and their microenvironment[J].Matrix Biol,2016,57/58:169-177.doi:10.1016/j.matbio.2016.07.010.
[6]Pickup MW,Mouw JK,Weaver VM.The extracellular matrix modulates the hallmarks of cancer[J].EMBO Rep,2014,15(12):1243-1253.doi:10.15252/embr.201439246.
[7]樊江浩,刘揆亮,吴静.蛋白多糖在肿瘤血管生成中的作用[J].临床与病理杂志,2016,36(4):515-519.doi:10.3978/j.issn.2095-6959.2016.04.032.Fan JH,Liu KL,Wu J.The roles of proteoglycans in tumor angiogenesis[J].International Journal of Pathology and C l i n i c a l M e d i c i n e,2016,36(4):515-519.d o i:10.3978/j.issn.2095-6959.2016.04.032.
[8]Raglow Z,Thomas SM.Tumor matrix protein collagen XIα1in cancer[J].Cancer Lett,2015,357(2):448-453.doi:10.1016/j.canlet.2014.12.011.
[9]Chen P,Cescon M,Bonaldo P.Collagen VI in cancer and its biological mechanisms[J].Trends Mol Med,2013,19(7):410-417.doi:10.1016/j.molmed.2013.04.001.
[10]Fang M,Yuan J,Peng C,et al.Collagen as a double-edged sword in tumor progression[J].Tumour Biol,2014,35(4):2871-2882.doi:10.1007/s13277-013-1511-7.
[11]杨程显,李戈,张立颖.胶原蛋白Ⅳ在肿瘤领域的研究进展[J].重庆医学,2015,44(32):4586-4588.doi:10.3969/j.issn.1671-8348.2015.32.044.Yang CX,Li G,Zhang LY.Research progress of CollagenⅣin tumors[J].Chongqing Medicine,2015,44(32):4586-4588.doi:10.3969/j.issn.1671-8348.2015.32.044.
[12]Li J,Ding Y,Li A.Identification of COL1A1 and COL1A2 as candidate prognostic factors in gastric cancer[J].World J Surg Oncol,2016,14(1):297.doi:10.1186/s12957-016-1056-5.
[13]Wang Q,Yu J.MiR-129-5p suppresses gastric cancer cell invasion and proliferation by inhibiting COL1A1[J].Biochem Cell Biol,2018,96(1):19-25.doi:10.1139/bcb-2016-0254.
[14]Rong L,Huang W,Tian S,et al.COL1A2 is a Novel Biomarker to Improve Clinical Prediction in Human Gastric Cancer:Integrating Bioinformatics and Meta-Analysis[J].Pathol Oncol Res,2018,24(1):129-134.doi:10.1007/s12253-017-0223-5.
[15]Huang R,Gu W,Sun B,et al.Identification of COL4A1 as a potential gene conferring trastuzumab resistance in gastric cancer based on bioinformatics analysis[J].Mol Med Rep,2018,17(5):6387-6396.doi:10.3892/mmr.2018.8664.
[16]Li A,Li J,Lin J,et al.COL11A1 is overexpressed in gastric cancer tissues and regulates proliferation,migration and invasion of HGC-27 gastric cancer cells in vitro[J].Oncol Rep,2017,37(1):333-340.doi:10.3892/or.2016.5276.
[17]李艳,黄祥,伊航,等.Smad4和NF-κBp65蛋白在肝癌组织中的表达及意义[J].中国普通外科杂志,2018,27(7):934-938.doi:10.3978/j.issn.1005-6947.2018.07.019.Li Y,Huang X,Yi H,et al.Expressions of Smad4 and NF-κBp65proteins in liver cancer tissue and their significance[J].Chinese Journal of General Surgery,2018,27(7):934-938.doi:10.3978/j.issn.1005-6947.2018.07.019.
[18]Lei H,Gao Y,Xu X.LncRNA TUG1 infl uences papillary thyroid cancer cell proliferation,migration and EMT formation through targeting miR-145[J].Acta Biochim Biophys Sin(Shanghai),2017,49(7):588-597.doi:10.1093/abbs/gmx047.
[19]吴至佛,姚晓艺,汪灵,等.紫杉醇诱导三阴性乳腺癌细胞自噬相关蛋白LC3的表达及其作用[J].中国普通外科杂志,2018,27(6):732-739.doi:10.3978/j.issn.1005-6947.2018.06.012.Wu ZF,Yao XY,Wang L,et al.Paclitaxel induced expression of autophagy-associated protein LC3 in triple negative breast cancer cells and its action[J].Chinese Journal of General Surgery,2018,27(6):732-739.doi:10.3978/j.issn.1005-6947.2018.06.012.
[20]Cui J,Chen Y,Chou WC,et al.An integrated transcriptomic and computational analysis for biomarker identification in gastric cancer[J].Nucleic Acids Res,2011,39(4):1197-1207.doi:10.1093/nar/gkq960.
[21]Kawakami H,Okamoto I.MET-targeted therapy for gastric cancer:the importance of a biomarker-based strategy[J].Gastric Cancer,2016,19(3):687-695.doi:10.1007/s10120-015-0585-x.
[22]Song Z,Wu Y,Yang J,et al.Progress in the treatment of advanced gastric cancer[J].Tumour Biol,2017,39(7):1010428317714626.doi:10.1177/1010428317714626.
[23]Zhuo C,Li X,Zhuang H,et al.Elevated THBS2,COL1A2,and SPP1 Expression Levels as Predictors of Gastric Cancer Prognosis[J].Cell Physiol Biochem,2016,40(6):1316-1324.doi:10.1159/000453184.
[24]Lee KS,Park GS,Hong SH,et al.Prognostic relevance of collagen XVIII expression in metastatic gastric carcinoma[J].Tumour Biol,2010,31(3):165-170.doi:10.1007/s13277-010-0022-z.
[25]Dabiri A,Baghaei K,Hashemi M,et al.Identification of differentially-expressed of Olfactomedin-related proteins 4 and COL11A1 in Iranian patients with intestinal gastric cancer[J].Gastroenterol Hepatol Bed Bench,2017,10(Suppl1):S62-69.
[26]Ruan HL,Hong RT,Xie HJ,et al.Signifi cance of elevated levels of collagen type IV and hyaluronic acid in gastric juice and serum in gastric cancer and precancerous lesion[J].Dig Dis Sci,2011,56(7):2001-2008.doi:10.1007/s10620-011-1571-8.
[27]Malik R,Lelkes PI,Cukierman E.Biomechanical and biochemical remodeling of stromal extracellular matrix in cancer[J].Trends Biotechnol,2015,33(4):230-236.doi:10.1016/j.tibtech.2015.01.004.
[28]Sangaletti S,Chiodoni C,Tripodo C,et al.The good and bad of targeting cancer-associated extracellular matrix[J].Curr Opin Pharmacol,2017,35:75-82.doi:10.1016/j.coph.2017.06.003.
[29]Jang M,Koh I,Lee JE,et al.Increased extracellular matrix density disrupts E-cadherin/β-catenin complex in gastric cancer cells[J].Biomater Sci,2018,6(10):2704-2713.doi:10.1039/c8bm00843d.