曹渤海,胡月明,田莉,王俊然,杨瑞东
CAO Bohai,HU Yueming,TIAN Li,WANG Junran,YANG Ruidong

• 1:唐山中心医院病理科
• 2:滦州市人民医院病理科

摘要(Abstract)：

目的 探讨Lin28B对三阴性乳腺癌侵袭转移的影响并分析其潜在机制。方法 经病理证实的80例三阴性乳腺癌患者、手术治疗后获取癌组织及癌旁组织，采用免疫组织化学法检测癌组织、癌旁组织中Lin28B表达、采用实时荧光定量-PCR(RT-PCR)法检测Let-7家族成员微小RNAs(miRNA)相对表达量，并比较两项指标在不同浸润程度、转移情况癌组织中的表达水平。结果 乳腺癌组织中Lin28B阳性率高于癌旁组织(P <0.05);随着肿瘤浸润深度的增加，乳腺癌组织中Lin28B阳性率依次增加(52.17%、74.36%、88.89%,P <0.05);有远处转移乳腺癌患者的肿瘤组织中Lin28B蛋白阳性率高于无远处转移患者(P <0.05)、有淋巴结转移乳腺癌患者肿瘤组织中Lin28B蛋白阳性率高于无淋巴结转移患者(P <0.05);乳腺癌组织中Let-7家族各成员miRNA相对表达量均低于癌旁组织(P <0.05)，随着浸润深度的增加，乳腺癌组织中Let-7家族成员miRNA相对表达量依次降低(P <0.05);乳腺癌有远处转移或淋巴结转移患者的Let-7家族成员miRNA相对表达量低于无转移患者(P <0.05)。结论 Lin28B与三阴性乳腺癌的侵袭及转移相关，其作用机制可能与过表达的Lin28B蛋白靶向调节(下调) Let-7家族成员表达水平有关。
Objective To investigate the effect of Lin28B on invasion and metastasis of triple negative breast cancer and its potential mechanism. Methods Breast cancer tissues and corresponding paracancerous tissues were obtained by surgery from 80 patients with pathologically verified triple-negative breast cancer. Immunohistochemistry( IHC) was used to detect Lin28B expression in cancer tissues and paracancerous tissues. Real-time fluorescent quantitative PCR( RTqPCR) was applied to detect the relative expression levels of Let-7 miRNA family members. The levels of Lin28B and Let-7 miRNA family members were compared among breast cancer tissues with different degree of invasion and metastasis. Results Lin28B-positive rate in breast cancer tissues was higher than that in paracancerous tissues( P < 0. 05). Lin28B-positive rate in breast cancer tissues was increased with the depth of invasion( 52. 17%,74. 36%,88. 89%; P < 0. 05). Lin28B-positive rate was higher in breast cancer tissues with distant metastasis than that without distant metastasis( P <0. 05),and it was higher in breast cancer tissues with lymph node metastasis than that without lymph node metastasis( P < 0. 05). The relative expression levels of Let-7 miRNA family members in breast cancer tissues were lower than those in paracancerous tissues( P < 0. 05). The relative expression levels of Let-7 miRNA family members in breast cancer tissue were decreased with the increase of invasion depth( P < 0. 05). The relative expression levels of Let-7 miRNA family members in patients with distant metastasis or lymph node metastasis of breast cancer were lower than that in patients without metastasis( P < 0. 05),Conclusion Lin28B is associated with invasion and metastasis of triple-negative breast cancer,and its mechanism may be related to Lin28B overexpression which downregulates the expression levels of Let-7 family members.

关键词(KeyWords)： 三阴性乳腺癌;浸润;转移;Lin28B;Let-7家族;微小RNAs
triple-negative breast cancer;infiltration;metastasis;Lin28B;Let-7 family;microRNAs(miRNA)

Abstract:

Keywords:

基金项目(Foundation): 河北省2021年度医学科学课题研究计划(20211657)

作者(Author): 曹渤海,胡月明,田莉,王俊然,杨瑞东
CAO Bohai,HU Yueming,TIAN Li,WANG Junran,YANG Ruidong

参考文献(References)：

• [1]马宇光，赵芳，王梦，等．三阴性乳腺癌术后骨转移与血清PRL、IL-1β以及BSP表达之间的关联探索[J]．中南医学科学杂志，2020,48(4):403-405．
• [2]SENNERSTAM R B,FRANZéN B S H,WIKSELL H OT,et al.Core-needle biopsy of breast cancer is associated with a higher rate of distant metastases 5 to 15 years after diagnosis than FNA biopsy[J].Cancer Cytopathol,2017,125(10):748-756．
• [3]邓超，卢俊宇，吴素华，等．消化道早癌内镜黏膜下剥离术的质量控制[J]．西南医科大学学报，2022,45(2):98-102．
• [4]张瑾，陈薇，刘蕾．2017年《NCCN乳腺癌筛查和诊断临床实践指南》(第1版)更新与解读[J]．中国全科医学，2017,20(24):2939-2943．
• [5]杨涛，马秀芬，毛红岩，等．TP与EC-T化疗方案在三阴性乳腺癌新辅助化疗中疗效与BRCA1突变关系[J]．现代肿瘤医学，2022,30(10):1776-1780．
• [6]杨云，张亮，李佳钋，等．Lin28B在重度子痫前期胎盘组织中的表达及其临床意义研究[J]．中国实用妇科与产科杂志，2019,35(6):681-685．
• [7]SIEGEL R L,MILLER K D,JEMAL A.Cancer Statistics,2018[J].CA Cancer J Clin,2018,68(1):7-30．
• [8]赵云飞，何姣，杨玲，等．乳腺癌组织中miR-502和HDAC3表达的相关性及其临床意义[J]．中南医学科学杂志，2021,49(4):447-451．
• [9]曹红，李雪红，周雪，等．基于计划行为理论的健康教育护理模式对康复期乳腺癌患者自我管理能力和癌因性疲乏的影响[J]．川北医学院学报，2021,36 (12):1663-1666．
• [10]KIM S H,PARK B O,KIM K,et al.Sjogren syndrome antigen B regulates LIN28-let-7 axis in caenorhabditis elegans and human[J].Biochim Biophys Acta Gene Regul Mech,2021,1864(3):194684．
• [11]SUN Z,YU H,ZHAO J,et al.LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells[J].Protein Cell,2022,13(7):490-512．
• [12]OH Y,PARK J,KIM J I,et al.Lin28B and miR-142-3p regulate neuronal differentiation by modulating Staufen1 expression[J].Cell Death Differ,2018,25(2):432-443．
• [13]陈少坚，林拥华，吴友谊，等．Lin28对肝癌Hep G2细胞5-Fu敏感性的影响及其分子机制[J]．中国肿瘤生物治疗杂志，2020,27(3):261-266．
• [14]李建华，韩玲，杨志良．miR-125b通过靶向致癌基因LIN28B调控肝细胞癌细胞的增殖和侵袭行为[J]．实用肿瘤杂志，2018,33(2):128-132．
• [15]LIN X,SHEN J,DAN P,et al.RNA-binding protein LIN28B inhibits apoptosis through regulation of the AKT2/FOXO3A/BIM axis in ovarian cancer cells[J].Signal Transduct Target Ther,2018,3(1):409-416．
• [16]郑俊全，伊索恒，武杰，等．富含亮氨酸重复序列免疫球蛋白样蛋白1、E-Cadherin和EGFR在胃癌中的表达和临床意义[J]．临床和实验医学杂志，2017,16(23):2329-2332．
• [17]ALAM M,AHMAD R,RAJABI H,et al.MUC1-C Induces the LIN28B→LET-7→HMGA2 axis to regulate self-renewal in NSCLC[J].Mol Cancer Res,2015,13(3):449-60．
• [18]MENEZES M R,BALZEAU J,HAGAN J P.3'RNA uridylation in epitranscriptomics,gene regulation,and disease[J].Front Mol Biosci,2018,13(5):61．
• [19]黄恩雨，马音晓，何志巍．异构酶Pin1生理特性与其在肿瘤中的作用研究进展[J]．西南医科大学学报，2022,45(3):262-266．
• [20]ALI A,BOUMA G J,ANTHONY R V,et al.The role of LIN28-let-7-ARID3B pathway in placental development[J].Int J Mol Sci,2020,21(10):3637．
• [21]XIONG H,SHEN J,CHEN Z,et al.H19/let-7/Lin28ceRNA network mediates autophagy inhibiting epithelialmesenchymal transition in breast cancer[J].Int J Oncol,2020,56(3):794-806．
• [22]张鹏飞，周保成，周哲，等．let-7d-5p调控HPV16阳性宫颈癌细胞侵袭、迁移及凋亡的分子机制[J]．分子诊断与治疗杂志，2020,12(7):892-896．
• [23]吕霄晗，林蓉．Lin28与肿瘤、心血管疾病及糖尿病[J]．中国临床药理学与治疗学，2022,27(2):205-211．
• [24]吴桐，张巧丽，齐雪维．肝细胞癌RNA结合蛋白功能和预后价值系统分析[J]．实用肝脏病杂志，2022,25(5):693-697．
• [25]CHEN Y,XIE C,ZHENG X,et al.LIN28/let-7/PD-L1pathway as a target for cancer immunotherapy[J].Cancer Immunol Res,2019,7(3):487-497．
• [26]OH J S,KIM J J,BYUN J Y,et al.Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras[J].Int J Radiat Oncol Biol Phys,2010,76(1):5-8.

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