上皮性卵巢癌组织中miR-199a-3p、COL12A1的表达及作用机制研究
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v2i5.3210
Abstract
卵巢恶性肿瘤的发病率及死亡率均较高。上皮性卵巢癌(epithelial ovarian cancer,EOC)占卵巢恶性肿瘤的85％-90％,其恶性程度高、病情发展迅速,仍然是妇科恶性肿瘤患者死亡的主要原因[1,2],由于其原发于盆腔深部,以前超声和糖链抗原125(CA125)检测是国内EOC常见的筛查手段[3],但超声诊断灵敏度以及特异度低,(CA)125在其他非卵巢恶性肿瘤及非肿瘤相关疾病中也有一定的阳性率,70%患者发现时已处于癌症晚期失去了最佳手术时机。最新研究显示,上皮性卵巢癌患者病死率仍然较高,5年生存率仅为40%-50%[4]。因其早期症状不明显,且进展迅速、易于播散等特点,通常确诊时大多数已进入中晚期阶段[5]。到目前为止,EOC的发病机制尚未研究透彻,近年来EOC的研究热点是分子机制的研究,并寻找其治疗EOC的方法。
Keywords
上皮性卵巢癌；miRNA-199a-3p；COL12A1
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[2] Siegel R L, Miller K D, Jemal A. Cancer statistics, 2016[J].CA Cancer J Clin,2016,66(1):7-30.
[3] 王丽华,陈福美,仲艳密,等.超声联合血清CA125对卵巢癌的诊断价值分析[J].中国临床医学影像杂志,2018,29(2):144-145.
[4] Siegel R L, Fedewa S A, Miller K D,et al.Cancer statistics for Hispanics/Latinos, 2015[J].CA Cancer J Clin,2015,65(6):457.
[5] Sakhuja S, Yun H, Pisu M, et al. Availability of healthcare resources and epithelial ovarian cancer stage of diagnosis and mortality among Blacks and Whites[J].J Ovarian Res,2017,10(1):57.
[6] Bartel D P.MicroRNAs:genomics,
[7] Iorio M V, Ferracin M, Liu C G, et al.MicroRNA gene expression deregulation
[8] Friedman R C, Farh K K, Burge C B,et al.Most mammalian mRNAs are conserved targets of microRNAs[J].
[9] Cheng A M, Byrom M W, Shelton J, et al. Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis[J].Nucl eic Acids Res, 2005,33(4):1290-1297.
[10] Wang W,Zhao E,Yu Y,et al.MiR-216a exerts tumor-suppressing functions in renal cell carcinoma by targeting TLR4[J]. Am J Cancer Res, 2018,8(3):476-488.
[11] Xu B, Zhang X, Wang S, et al. MiR-449a suppresses cell migration and invasion by targeting PLAGL2 in breast cancer[J]. Pathol Res Pract, 2018,214(5):790-795.
[12] Zhang H, Zuo Z, Lu X, et al. MiR-25 regulates apoptosis by targeting Bim in human ovarian cancer[J]. Oncol Rep, 2012,27(2):594-598.
[13] Resnick K E, Alder H, Hagan J P,et al.The detection of differentially expressed microRNAs from the serum of ovarian cancer patients using a novel real-time PCR platform[J]. Gynecol Oncol, 2009,112(1):55-59.
[14] 徐利坚.卵巢癌血清miRNA的筛选及其在早期诊断中的应用意义[D].浙江理工大学生物化学与分子生物学,2012.
[15] Xu Q,Liu L Z,Qian X,et al.MiR-145 directly targets p70S6K1in cancer cells to inhibit tumor growth and angi ogenesis[J].NucleicAcids Res,2012,40(2):774.
[16] Yang N, Kaur S, Volinia S, et al. MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer[J].CancerRes,2008,68(24):10314.
[17] Johnson S M,Grosshans H,Shingara J, et al. RAS is regulated by the let-7 microRNAfamily[J].Cell,2005,120(5):635.
[18] Yang C, Cai J, Wang Q, et al. Epigenetic silencing of miR-130b in ovarian cancer promotes the development of multidrug resistance by targeting colony-stimulating factor 1[J].Gynecol Oncol, 2012,124(2):325-334.
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[21] Mezzanzanica D,Canevari S,Cecco L D, et al. miRNA control of apoptotic programs:focus on ovarian cancer[J].Expert Rev Mol Diagn,2011,11(3):277-286.
[22] Lu L, Schwartz P, Scarampi L, et al. MicroRNA let-7a: a potential marker for selection of paclitaxel in ovarian cancer management[J]. Gynecol Oncol, 2011,122(2):366-371.
[23] Marchini S,Cavalieri D, Fruscio R, et al. Association between miR-200c and the survival of patients with stage I epithelial ovarian cancer:a retrospective study of two independent tumour tissue collections[J].LancetOncol,2011,12(3):273.
[24] Kim T H, Kim Y K, Kwon Y, et al. Deregulation of miR-519a, 153, and 485-5p and its clinicopathological relevance in ovarian epithelial tumours [J].Histopathology,2010,57(5):734-743.
[25] Gerecke D R, Olson P F, Koch M, et al. Complete primary structure of two splice variants of collagen XII, and assignment of alpha 1(XII) collagen (COL12A1),alpha 1(IX)collagen (COL9A1), and alpha 1(XIX) collagen(COL19A1)to human chromosome 6q12-q13[J].Genomics, 1997,41(2):236-242.
[26] Hicks D, Farsani G T, Laval S, et al. Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy[J]. Hum Mol Genet,2014,23(9):2353-2363.
[27] Sun F,Ding W,He J H,et al.Stomatin -like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival[J]. BMC Cancer, 2015,15:746.
[28] Zhao H, Ljungberg B, Grankvist K, et al. Gene expression profiling predicts survival in conventional renal cell carcinoma[J]. PLoS Med, 2006,3(1):e13.
[29] Ramaswamy S, Ross K N, Lander E S, et al. A molecular signature of metastasis in primary solid tumors[J]. Nat Genet, 2003,33(1):49-54.
[30] Storlazzi C T, Wozniak A, Panagopoulos I, et al. Rearrangement of the COL12A1 and COL4A5 genes in subungual exostosis:molecular cytogenetic delineation of the tumor-specific translocationt(X;6)(q13-14;q22)[J].Int J Cancer,2006,118(8):1972-1976.
[31] Januchowski R, Swierczewska M, Sterzynska K,et al.Increased Expression of Several Collagen Genes is Associated with Drug Resistance in Ovarian Cancer Cell Lines[J].J Cancer,2016,7(10):1310.
[32] Verghese E T, Drury R, Green C A, et al. MiR-26b is down-regulated in carcinoma-associated fibroblasts from ER-positive breast cancers leading to enhanced cell migration and invasion[J]. J Pathol, 2013,231(3):388-399.
[33] Mikula M, Rubel T, Karczmarski J, et al.Integrating proteomic and transcrip tomic high-throughput surveys for search of new biomarkers of colon tumors[J].Funct Integr Genomics,2011,11(2):215-224.
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