Expression and significance of matrix metalloproteinase-9 and Raf kinase inhibitor protein mRNA in prostate cancer
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摘要: 目的:观察Raf激酶抑制蛋白(RKIP)、基质金属蛋白酶-9(MMP-9) mRNA在前列腺癌(PCa)中的表达变化,并探讨其临床意义。方法:采用qPCR法检测PCa及良性前列腺增生(BPH)组织中RKIP、MMP-9mRNA的表达,并分析二者表达与临床病理特征关系及二者之间的相关性。结果:RKIP mRNA在PCa组织中相对表达量显著低于BPH组织(P<0.01);MMP-9mRNA在PCa组织中相对表达量显著高于BPH组织(P<0.01)。RKIP mRNA在PCa组织中相对表达量随着Gleason评分的增高而降低(均P<0.05);在PCa组织T2N0M0期以内的无侵袭转移组中的相对表达量高于侵袭转移组(P<0.05)。MMP-9mRNA在PCa组织中相对表达量随着Gleason评分的增高而增高(P<0.05);在PCa组织T2N0M0期以内的无侵袭转移组中的相对表达量低于侵袭转移组(P<0.01)。RKIP mRNA与MMP-9mRNA的表达呈负相关(P<0.01)。结论:RKIP mRNA低表达与MMP-9mRNA高表达可能与PCa的发生发展有关,同时RKIP mRNA与MMP-9mRNA表达之间具有相关性,RKIP可能通过调控MMP-9从而促进PCa的发生发展。Abstract: Objective: To investigate the expression and significance of Raf kinase inhibitor protein (RKIP) and matrix metalloproteinase-9 (MMP-9) mRNA in prostate cancer.Method: Real-time fluorescence quantitative PCR (qPCR) was used to determine the expressions of RKIP and MMP-9mRNA in prostate cancer and benign prostatic hyperplasia tissues, and the relationship between the expression and patients'clinicopathologic characteristics and the correlation between the two were analyzed.Result: The relative expression level of RKIP mRNA in prostate cancer tissues was lower than that in prostate hyperplasia tissues (P<0.01).The relative expression level of MMP-9mRNA in prostate cancer tissues was higher than that in prostate hyperplasia tissues (P<0.01).The relative expression level of RKIP mRNA in prostate cancer tissues decreased with the increase of Gleason score (P<0.05).The relative expression level of the non-metastatic group within T2N0M0was higher than that of the invasive and metastatic group (P<0.05).The relative expression level of MMP-9mRNA in prostate cancer tissues increased with the increase of Gleason score (P<0.05).The relative expression level of the non-metastatic group within T2N0M0was lower than that of the invasive and metastatic group (P<0.01).RKIP mRNA was negatively correlated with MMP-9mRNA (P<0.01).Conclusion: Low expression of RKIP mRNA and high expression of MMP-9may be related to the tumorigensis and progression of prostate cancer, and the expression of RKIP mRNA and MMP-9mRNA are correlated.RKIP may promote the occurrence and development of prostate cancer by regulating MMP-9.
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[1] 杨进益, 杨明州, 魏伟, 等.前列腺癌发生发展的流行病学研究进展[J].临床泌尿外科杂志, 2017, 32 (9):721-725.
[2] Chen W, Sun K, Zheng R, et al.Cancer incidence and mortality in China, 2014[J].Chin J Cancer Res, 2018, 30 (1) 1-12.
[3] Yesilkanal A E, Rosner M R.Targeting Raf Kinase Inhibitory Protein Regulation and Function[J].Cancer (Basel), 2018.
[4] Dai H, Chen H, Liu W, et al.Effects of Raf kinase inhibitor protein expression on pancreatic cancer cell growth and motility:an in vivo and in vitro study[J].J Cancer Res Clin Oncol, 2016, 142 (10):2107-2117.
[5] Deiss K, Kisker C, Lohse M J, et al.Raf kinase inhibitor protein (RKIP) dimer formation controls its target switch from Raf1 to G protein-coupled receptor kinase (GRK) 2[J].J Biol Chem, 2012, 287 (28):23407-23417.
[6] Tang H, Park S, Sun S C, et al.RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling components of the IkappaB kinase complex[J].FEBSLett, 2010, 584 (4):662-668.
[7] AI-Mulla F, Bitar M S, AI-Maghrebi M, et al.Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3β[J].Cancer Res, 2011, 71 (4):1334-1343.
[8] Wang A, Duan G, Zhao C, et al.Reduced RKIP expression levels are associated with frequent non-small cell lung cancer metastasis and STAT3 phosphorylation and activation[J].Oncol Lett, 2017, 13 (5):3039-3045.
[9] Patruno A, Pesce M, Marrone A, et al.Activity of matrix metallo proteinases (MMPs) and the tissue inhibitor of MMP (TIMP) -1in electromagnetic field-exposed THP-1cells[J].J Cell Physiol, 2012, 227 (6):2767-2774.
[10] Visse R, Nagase H.Matrix metalloproteinases and tissue inhibitor of metalloproteinases:structure, function, and biochemistry[J].Circ Res, 2003, 92 (8):827-839.
[11] Huang H.Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomaker and MMP-9 Biosensor:recent Advances[J].Sensors (Basel), 2018 (10):3249-3249.
[12] 高放, 张凤梅, 李胜水, 等.膀胱良、恶性上皮肿瘤中MMP-9的表达及临床意义[J].现代肿瘤医学, 2014, 22 (1):134-136.
[13] Zhang Y, Guan X Y, Dong B, et al.Expression of MMP-9and WAVE3 in colorectal cancer and its relationship to clinicopathological features[J].J Cancer Res Clin Oncol, 2012, 138 (12):2035-2044.
[14] 臧家兵, 王洪远, 王伟.COX和MMP-9在皮肤鳞状细胞癌中的表达[J].中国麻风皮肤病杂志, 2012, 28 (7):482-484.
[15] Klassen L M B, Chequin A, Manica G C, et al.MMP9 gene expression regulation by intragenic epigenetic modifications in breast cancer[J].Gene, 2018, 642:461-466.
[16] Kim G E, Kim N I, Lee J S, et al.Reduced RKIP Expression is Associated With Breast Neoplastic Progression and is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma[J].Appl Immunohistochem Mol Morphol, 2017, 25 (7):467-474.
[17] Cardile V, Malaponte G, Loreto C, et al.Raf kinase inhibitor protein (RKIP) and phospho-RKIP expression in melanomas[J].Acta Histochem, 2013, 115 (8):795-802.
[18] Zaravinos A, Chatziioannou M, Lambrou G I, et al.Implication of RAF and RKIP genes in urinary bladder cancer[J].Pathol Oncol Res, 2011, 17 (2):181-190.
[19] Xu H, Wang X, Shen W, et al.The expression and significance of RKIP in lung squamous cell carcinoma tissues[J].Zhongguo Fei Ai Za Zhi, 2011, 14 (3):194-198.
[20] 赵鹏程, 杨栋, 任乐, 等.RKIP对前列腺癌PC3细胞侵袭、转移的影响及机制[J].现代泌尿外科杂志, 2018, 23 (12):956-960, 974.
[21] Du Y, Zhu H, Liu X, et al.MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in prostate Cancer via Targeting RKIP[J].Cell Physiol Biochem, 2017, 41 (3):1135-1146.
[22] Keller E T.Role of Raf Kinase Inhibitor Protein in Pathophysiology of Prostate Cancer[J].For Immunopathol Dis Therap, 2011, 2 (1):89-94.
[23] Xue Q, Cao L, Chen X Y, et al.High expression of MMP9 in glioma affects cell proliferation and is associated with patient survival rates[J].Oncol Lett, 2017, 13 (3):1325-1330.
[24] Klimczak-Bitner A A, Kordek R, Bitner J, et al.Expression of MMP9, SERPINE1 and miR-134as prognostic factors in esophageal cancer[J].Oncol Lett, 2016, 12 (5):4133-4138.
[25] Reis S T, Pontes-Junior J, Antunes A A, et al.MMP-9overexpression due to TIMP-1and RECK underexpression is associated with prognosis in prostate cancer[J].Int J Biol Markers, 2011, 26 (4), 255-261.
[26] Trudel D, Fradet Y, Meyer F, et al.Matrix metalloproteinase 9is associated with Gleason score in prostate cancer but not with prognosis[J].Hum Pathol, 2010, 41 (12):1694-1701.
[27] Zaracinos A, Bonavida B, Chatzaki E, et al.RKIP:A key Regulator in Tumor Metastasis Initiation and Resistance to Apotosis:Therapeutic Targeting and Impact[J].Cancers (Basel), 2018.
[28] Datar I, Feng J, Qiu X, et al.RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13[J].PLoS One, 2015, 10 (8):e0134494.
[29] Lei X, Chang L, Ye W, et al.Raf kinase inhibitor protein (RKIP) inhibits the cell migration and invasion in human glioma cell lines in vitro[J].Int J Clin Exp Pathol, 2015, 8 (11):14214-14220.
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