miR-155在弥漫大B细胞淋巴瘤组织中的表达及其对细胞生物学特性的影响
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摘要
目的:探讨miR-155在弥漫大B细胞淋巴瘤(DLBCL)组织中的表达,以及转染miR-155抑制物对DLBCL细胞生物学特性的影响。方法:选取2013年4月至2017年12月在本院接受治疗的DLBCL患者76例,同时选取因淋巴结反应性增生就诊的40例患者作为对照组。取2组患者组织标本。培养DB细胞并将其分为miR-155抑制物组、阴性对照组和空白组。使用实时荧光定量PCR技术检测DLBCL组和对照组组织及细胞中miR-155的表达;应用MTT法检测细胞的增殖能力,流式细胞术检测细胞凋亡情况;Transwell法检测细胞迁移和侵袭能力。结果:DLBCL患者组织中miR-155相对表达量(1.93±0.16)明显高于对照组(1.01±0.09)(t=33.991,P=0.000)。miR-155表达量在乳酸脱氢酶水平异常、BCL-2~+、MUM1~+和Ki-67≥50%、病理类型非GC型、Ann Arbor分期Ⅲ-Ⅳ期、结外病变数≥2和IPI评分3-5分的DLBCL患者组织中升高(P<0.05);miR-155抑制物组细胞中miR-155相对表达量明显低于阴性对照组和空白组(P<0.05),miR-155抑制物组细胞在培养24、48、72和96 h时吸光度A值明显低于阴性对照组和空白组(P<0.05),而细胞凋亡率则明显高于阴性对照组和空白组(P<0.05);miR-155抑制物组迁移细胞数和侵袭细胞数明显低于阴性对照组和空白组(P<0.05)。结论:miR-155在DLBCL患者组织中呈高表达,且与肿瘤恶性程度和侵袭进展有关,在特异性抑制DB细胞中miR-155的表达可减少细胞增殖,加速细胞凋亡,抑制细胞迁移及侵袭。
Objective: To investigate the expression of miR-155 in patients with diffuse large B-cell lymphoma(DLBCL), and to explore the effect of transfection of miR-155 inhibitor on the biological characteristics of DLBCL cells.Methods: A total of 76 patients with DLBCL treated in our hospital were selected from April 2013 to December 2017.In the same time, 40 cases of lymph node reactive hyperplasia (LNRH) were selected as control group. DB cells were cultured and divided into miR-155 inhibitor, negative control and blank groups. The expressions of miR-155 in DLBCL,negative and blank control groups were detected by using real-time PCR, the cell proliferation was detected by MTT assay, the apoptosis was detected by flow cytometry, and the cell migration and invasion were detected by Transwell assay. Results: The relative expression level of miR-155 in tissues of DLBCL patients was significantly higher than that in tissne of controls (1.93±0.16 vs 1.01±0.09) (t = 33.991, P = 0.000). The expression level of miR-155 increased (P < 0.05) in DLBCL patients with LDH level abnormarity, BCL-2~+, MUM1~+, Ki-67≥ 50%, non-GC type, Ann Arbor stage Ⅲ-Ⅳ, extranodal lesion number≥ 2 and IPI score 3-5. The relative expression level of miR-155 in the miR-155 inhibitor group was lower than that in the negative control group and the blank group (P<0.05). The absorbance (A) values at 24, 48, 72 and 96 h of culture in the miR-155 inhibitor group were lower than those in the negative control groupand the blank group (P< 0.05), while the apoptotic rate was higher than that in the negative control group and the blank group (P< 0.05). Both the migrating cells and invading cell number in the miR-155 inhibitor group were lower than those in the negative control group and the blank group (P < 0.05). Conclusion: The miR-155 highly expresses in DLBCL tissue, which relates with tumor malignancy and invasion progression. The specific inhibition of miR-155 expression in DB cells can reduce cell proliferation, accelerate cell apoptosis, and inhibit cell migration and invasion.
Objective: To investigate the expression of miR-155 in patients with diffuse large B-cell lymphoma(DLBCL), and to explore the effect of transfection of miR-155 inhibitor on the biological characteristics of DLBCL cells.Methods: A total of 76 patients with DLBCL treated in our hospital were selected from April 2013 to December 2017.In the same time, 40 cases of lymph node reactive hyperplasia (LNRH) were selected as control group. DB cells were cultured and divided into miR-155 inhibitor, negative control and blank groups. The expressions of miR-155 in DLBCL,negative and blank control groups were detected by using real-time PCR, the cell proliferation was detected by MTT assay, the apoptosis was detected by flow cytometry, and the cell migration and invasion were detected by Transwell assay. Results: The relative expression level of miR-155 in tissues of DLBCL patients was significantly higher than that in tissne of controls (1.93±0.16 vs 1.01±0.09) (t = 33.991, P = 0.000). The expression level of miR-155 increased (P < 0.05) in DLBCL patients with LDH level abnormarity, BCL-2~+, MUM1~+, Ki-67≥ 50%, non-GC type, Ann Arbor stage Ⅲ-Ⅳ, extranodal lesion number≥ 2 and IPI score 3-5. The relative expression level of miR-155 in the miR-155 inhibitor group was lower than that in the negative control group and the blank group (P<0.05). The absorbance (A) values at 24, 48, 72 and 96 h of culture in the miR-155 inhibitor group were lower than those in the negative control groupand the blank group (P< 0.05), while the apoptotic rate was higher than that in the negative control group and the blank group (P< 0.05). Both the migrating cells and invading cell number in the miR-155 inhibitor group were lower than those in the negative control group and the blank group (P < 0.05). Conclusion: The miR-155 highly expresses in DLBCL tissue, which relates with tumor malignancy and invasion progression. The specific inhibition of miR-155 expression in DB cells can reduce cell proliferation, accelerate cell apoptosis, and inhibit cell migration and invasion.
引文
1何志媛,谢双锋,聂大年,等. mPGES-1、NF-κB p65在弥漫大B细胞淋巴瘤中的表达及临床意义.中山大学学报(医学版), 2018; 39(1):73-81.
2 杨融辉,李诗文,沈静,等.来那度胺治疗弥漫大B细胞淋巴瘤的进展.现代肿瘤医学, 2018; 26(1):120-123.
3 Hong J, Kim SJ, Chang MH, et al. Improved prognostic stratification using NCCN-and GELTAMO-international prognostic index in patients with diffuse large B-cell lymphoma. Oncotarget, 2017;8(54):92171-92182.
4 Biggar KK, Storey KB. Functional impact of microRNA regulation in models of extreme stress adaptation. J Mol Cell Biol, 2018;10(2):93-101.
5 Hosseinahli N, Aghapour M, Duijf PHG, et al. Treating cancer with microRNA replacement therapy:A literature review. J Cell Physiol,2018; 233(8):5574-5588.
6 Testa U, Pelosi E, Castelli G, et al. miR-146 and miR-155:two key modulators of immune response and tumor development. Noncoding RNA, 2017; 3(3)doi:10.3390/ncrna3030022.
7 史晋叔,张娟. miR-155在弥漫性大B细胞淋巴瘤发病中的作用及可能机制.中国实验血液学杂志, 2014; 22(3):869-872.
8 Sabattini E, Bacci F, Sagramoso C, et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008:an overview. Pathologica, 2010; 102(3):83-87.
9 Till BG. Maintenance therapy in diffuse large B cell lymphoma and mantle cell lymphoma. Curr Treat Options Oncol, 2018; 19(9):45.
10 Wang J, Zhang Y, Liu X, et al. Annexin A5 inhibits diffuse large B-cell lymphoma cell invasion and chemoresistance through phosphatidylinositol 3-kinase signaling. Oncol Rep, 2014;32(6):2557-2563.
11 Laengsri V, Kerdpin U, Plabplueng C, et al. Cervical cancer markers:epigenetics and microRNAs. Lab Med, 2018; 49(2):97-111.
12 蔡婷婷,王菊勇,杜志华,等. microRNA-155与恶性肿瘤的研究进展.现代肿瘤医学, 2016; 24(14):2314-2318.
13 马莎英,李中福,韩继明,等.胃癌组织、癌旁组织及胃癌细胞系中miR-155表达水平及其与病理参数和临床疗效关系分析.肿瘤药学, 2017; 7(6):697-701.
14 Kim S, Lee E, Jung J, et al. microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene, 2018; 37(22):2982-2991.
15 Liu N, Jiang F, Han XY, et al. MiRNA-155 promotes the invasion of colorectal cancer SW-480 cells through regulating the Wnt/β-catenin. Eur Rev Med Pharmacol Sci, 2018; 22(1):101-109.
16 史晋叔,张娟. miR-155在弥漫性大B细胞淋巴瘤发病中的作用及可能机制.中国实验血液学杂志, 2014; 22(3):869-872.
2 杨融辉,李诗文,沈静,等.来那度胺治疗弥漫大B细胞淋巴瘤的进展.现代肿瘤医学, 2018; 26(1):120-123.
3 Hong J, Kim SJ, Chang MH, et al. Improved prognostic stratification using NCCN-and GELTAMO-international prognostic index in patients with diffuse large B-cell lymphoma. Oncotarget, 2017;8(54):92171-92182.
4 Biggar KK, Storey KB. Functional impact of microRNA regulation in models of extreme stress adaptation. J Mol Cell Biol, 2018;10(2):93-101.
5 Hosseinahli N, Aghapour M, Duijf PHG, et al. Treating cancer with microRNA replacement therapy:A literature review. J Cell Physiol,2018; 233(8):5574-5588.
6 Testa U, Pelosi E, Castelli G, et al. miR-146 and miR-155:two key modulators of immune response and tumor development. Noncoding RNA, 2017; 3(3)doi:10.3390/ncrna3030022.
7 史晋叔,张娟. miR-155在弥漫性大B细胞淋巴瘤发病中的作用及可能机制.中国实验血液学杂志, 2014; 22(3):869-872.
8 Sabattini E, Bacci F, Sagramoso C, et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008:an overview. Pathologica, 2010; 102(3):83-87.
9 Till BG. Maintenance therapy in diffuse large B cell lymphoma and mantle cell lymphoma. Curr Treat Options Oncol, 2018; 19(9):45.
10 Wang J, Zhang Y, Liu X, et al. Annexin A5 inhibits diffuse large B-cell lymphoma cell invasion and chemoresistance through phosphatidylinositol 3-kinase signaling. Oncol Rep, 2014;32(6):2557-2563.
11 Laengsri V, Kerdpin U, Plabplueng C, et al. Cervical cancer markers:epigenetics and microRNAs. Lab Med, 2018; 49(2):97-111.
12 蔡婷婷,王菊勇,杜志华,等. microRNA-155与恶性肿瘤的研究进展.现代肿瘤医学, 2016; 24(14):2314-2318.
13 马莎英,李中福,韩继明,等.胃癌组织、癌旁组织及胃癌细胞系中miR-155表达水平及其与病理参数和临床疗效关系分析.肿瘤药学, 2017; 7(6):697-701.
14 Kim S, Lee E, Jung J, et al. microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer. Oncogene, 2018; 37(22):2982-2991.
15 Liu N, Jiang F, Han XY, et al. MiRNA-155 promotes the invasion of colorectal cancer SW-480 cells through regulating the Wnt/β-catenin. Eur Rev Med Pharmacol Sci, 2018; 22(1):101-109.
16 史晋叔,张娟. miR-155在弥漫性大B细胞淋巴瘤发病中的作用及可能机制.中国实验血液学杂志, 2014; 22(3):869-872.