miR-139-5p在小细胞肺癌组织中的表达及其临床意义

doi:10.13481/j.1671-587x.20160520

吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (05): 942-948.doi: 10.13481/j.1671-587x.20160520

miR-139-5p在小细胞肺癌组织中的表达及其临床意义

刘换新¹, 张国祥¹, 郭琳琅², 唐松山³

1. 武警广东总队医院病理科, 广东广州 510507;
2. 南方医科大学附属珠江医院病理科, 广东广州 510282;
3. 广东药学院生化与分子生物学教研室, 广东广州 510006

收稿日期:2015-07-30 出版日期:2016-09-28 发布日期:2016-09-29
通讯作者: 郭琳琅,主任医师,教授,博士研究生导师(Tel:020-62783358;E-mail:linlanggg@yahoo.com) E-mail:linlanggg@yahoo.com
作者简介:刘换新(1969-),男,湖北省广济县人,副主任医师,医学博士,主要从事临床病理诊断及肿瘤多药耐药方面的研究。
基金资助:
国家自然科学基金资助课题（81172241）；广东省科技厅自然科学基金资助课题（2014A030313589）

Expression of miR-139-5p in small cell lung cancer tissue and its clinical significance

LIU Huanxin¹, ZHANG Guoxiang¹, GUO Linlang², TAN Songshan³

1. Department of Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China;
2. Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China;
3. Deparment of Biochemistry and Molecular Biology, Guangdong College of Pharmacy, Guangzhou 510006, China

Received:2015-07-30 Online:2016-09-28 Published:2016-09-29

摘要/Abstract

摘要：

目的：探讨miR-139-5p在小细胞肺癌组织中的表达及其临床意义，阐明miR-139-5p在小细胞肺癌发生发展中的作用。方法：采用细胞生长、凋亡及周期实验检测miR-139-5p的生物学功能；实时荧光定量PCR法检测50例小细胞肺癌患者癌组织及癌旁正常组织中miR-139-5p的表达，结合临床资料分析其在临床中的作用。结果：miR-139-5p在小细胞肺癌组织中的表达水平低于正常肺组织（P<0.01）；转染miR-139-5p mimics后能够明显上调细胞中miR-139-5p的表达，差异有统计学意义（P<0.01）。与对照组比较，上调miR-139-5p的表达后细胞的增殖能力降低（P<0.01），G₁期细胞明显增多（P<0.05），细胞周期发生G₀/G₁期阻滞。单因素分析，miR-139-5p的表达与患者的性别和年龄无关（P>0.05），miR-139-5p在局限期（LD）患者中的表达较广泛期（ED）患者低，两者的miR-139-5p表达率比较差异有统计学意义（χ²=10.546，P=0.001）；miR-139-5p在耐药患者中的表达较化疗敏感患者增高（χ²=7.025，P=0.008）。miR-139-5p在存活患者中的表达较死亡患者降低（χ²=7.697，P=0.006）；Cox回归分析，疾病分期和miR-139-5p的表达可作为小细胞肺癌独立的预后因子。结论：miR-139-5p通过抑制细胞增殖、促进细胞凋亡及诱导细胞周期阻滞参与调节小细胞肺癌发生发展，可作为评估小细胞肺癌患者临床预后的靶基因。

关键词: 癌, 小细胞肺, 实时荧光定量聚合酶链式反应, miR-139-5p

Abstract:

Objective: To explore the expression of miR-139-5p in small cell lung cancer (SCLC)tissue and its clinical significance,and to clarify the role of miR-139-5p in the occurrence and development of SCLC. Methods: The biological function of miR-139-5p was examined by cell growth, apoptosis and cell cycle analysis.The expressions of miR-139-5p in 50 cases of cancer tissue and paracarcinoma normal tissue were examined by QRT-PCR. Combined with the clinical data,the role of miR-139-5p in clinic was anzlyzed. Results: The expression level of miR-139-5p in SCLC tumor tissue was lower than that in normal lung tissue (P<0.01). The expression level of miR-139-5p in the cells was un-regulated significantly after transferred miR-139-5p mimics(P<0.01).Compared with control group,the proliferation abilitiy of cells was reduced after up-regulating the expression of miR-139-5p (P<0.01),the number of cells at G₁ phase was increased(P<0.05),and the cells were arrested at G₀/G₁ phase. The miR-139-5p expression was not associated with gender and age(P>0.05). The expression level of miR-139-5p in the patient at LD stage was lower than that of the patients at ED stage (P<0.01).The expression level of miR-139-5p in the resistant patients was higher than that of the patients sensitive to chemotherappy(P<0.01).The expression level of miR-139-5p in the survival patients was lower than that in the death patients(P<0.01). Cox regression analysis indicated that miR-139-5p expression and disease stage were the independent prognostic factors for SCLC. Conclusion: miR-139-5p in participates in the occurrence and development of SCLC by inhibiting the cell proliferation, promoting apoptosis and inducing the cell cycle arrest;it may be used as a target gene to evaluate the prognosis of SCLC patients.

Key words: cancer,small cell lung, real-time quantitative polymerase chain reaction, miR-139-5p

中图分类号:

R734.2

刘换新, 张国祥, 郭琳琅, 唐松山. miR-139-5p在小细胞肺癌组织中的表达及其临床意义[J]. 吉林大学学报(医学版), 2016, 42(05): 942-948.

LIU Huanxin, ZHANG Guoxiang, GUO Linlang, TAN Songshan. Expression of miR-139-5p in small cell lung cancer tissue and its clinical significance[J]. Journal of Jilin University Medicine Edition, 2016, 42(05): 942-948.

参考文献

[1] Bai Y, Sun Y, Peng J, et al.Overexpression of secretagogin inhibits cell apoptosis and induces chemoresistance in small cell lung cancer under the regulation of miR-494[J].Oncotarget,2014,5(17):7760-7775.

[2] Fang S, Gao H, Tong Y, et al.Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells[J].Lab Invest,2016,96(1):60-68.

[3] Fang S, Zeng X, Zhu W, et al.Zinc finger E-box-binding homeobox 2(ZEB2) regulated by miR-200b contributes to multi-drug resistance of small cell lung cancer[J].Exp Mol Pathol,2014,96(3):438-444.

[4] Huang C, Huang M, Chen W, et al.N-acetylglucosaminyltransferase V modulates radiosensitivity and migration of small cell lung cancer through epithelial-mesenchymal transition[J].FEBS J,2015,282(22):4295-4306.

[5] Brücher BL, Li Y, Schnabel P, et al.Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers[J].Clin Transl Med,2016,5(1):13.

[6] Sita-Lumsden A, Dart DA, Waxman J,et al.Circulating microRNAs as potential new biomarkers for prostate cancer[J].Br J Cancer,2013,108(10):1925-1930.

[7] Chi Y,Zhou D.MicroRNAs in colorectal carcinoma-from pathogenesis to therapy[J].J Exp Clin Cancer Res,2016,35(1):43.

[8] Pileczki V, Cojocneanu-Petric R, Maralani M, et al.MicroRNAs as regulators of apoptosis mechanisms in cancer[J].Clujul Med,2016,89(1):50-55.

[9] Dai S, Wang X, Li X, et al.MicroRNA-139-5p acts as a tumor suppressor by targeting ELTD1 and regulating cell cycle in glioblastoma multiforme[J].Biochem Biophys Res Commun,2015,467(2):204-210.

[10] Emmrich S, Engeland F, El-Khatib M, et al.miR-139-5p controls translation in myeloid leukemia through EIF4G2[J].Oncogene,2016,35(14):1822-1831.

[11] Watanabe K, Amano Y, Ishikawa R, et al.Histone methylation-mediated silencing of miR-139 enhances invasion of non-small-cell lung cancer[J].Cancer Med,2015,4(10):1573-1582.

[12] Li X, Zhu W, Chen Z, et al.Fibroblast growth factor-inducible 14 regulates cell growth and multidrug resistance of small-cell lung cancer through the nuclear factor-kappaB pathway[J].Anticancer Drugs,2014,25(10):1152-1164.

[13] Liu H, Wu X, Huang J, et al.miR-7 modulates chemoresistance of small cell lung cancer by repressing MRP1/ABCC1[J].Int J Exp Pathol,2015,96(4):240-247.

[14] Huang J, Peng J, Guo L.Non-coding RNA:a new tool for the diagnosis, prognosis, and therapy of small cell lung cancer[J].J Thorac Oncol,2015,10(1):28-37.

[15] Adams BD, Kasinski AL,Slack FJ.Aberrant regulation and function of microRNAs in cancer[J].Curr Biol,2014,24(16):R762-R776.

[16] Tung MC, Lin PL, Cheng YW, et al.Reduction of microRNA-184 by E6 oncoprotein confers cisplatin resistance in lung cancer via increasing Bcl-2[J].Oncotarget,2016.doi:10.18632/oncotarget.8708.[Epub ahead of print]

[17] Zou F, Mao R, Yang L, et al.Targeted deletion of miR-139-5p activates MAPK, NF-κB and STAT3 signaling and promotes intestinal inflammation and colorectal cancer[J].FEBS J,2016,283(8):1438-1452.

[18] Sun C, Sang M, Li S, et al.Hsa-miR-139-5p inhibits proliferation and causes apoptosis associated with down-regulation of c-Met[J].Oncotarget,2015,6(37):39756-39792.

[19] Zhang HD, Sun DW, Mao L, et al.MiR-139-5p inhibits the biological function of breast cancer cells by targeting Notch1 and mediates chemosensitivity to docetaxel[J].Biochem Biophys Res Commun,2015,465(4):702-713.

miR-139-5p在小细胞肺癌组织中的表达及其临床意义

Expression of miR-139-5p in small cell lung cancer tissue and its clinical significance

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 0

[1]	杨巍, 李明成. 人口腔鳞状细胞癌Tca8113细胞过表达WWOX基因的基因表达谱分析及WWOX基因的抑癌作用机制[J]. 吉林大学学报(医学版), 2018, 44(06): 1169-1173.
[2]	李丽静, 臧亚茹, 于文会, 梁君伟, 佟艳军. 化疗联合斑蝥酸钠维生素B6注射液对非小细胞肺癌患者的治疗效果及其机制[J]. 吉林大学学报(医学版), 2018, 44(06): 1286-1290.
[3]	袁虎勤, 李强. 水飞蓟素对人胃癌SGC 7901细胞增殖、迁移和侵袭的抑制作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(05): 988-993.
[4]	孟琳, 王璐, 布文奂, 丁鑫鑫, 高华丽, 王梓霖, 刘玉兰, 李琛, 孙宏晨. 小鼠骨髓间充质干细胞对人舌鳞状细胞癌Cal27细胞的归巢作用及其对Cal27细胞增殖和迁移的促进作用[J]. 吉林大学学报(医学版), 2018, 44(05): 891-896.
[5]	孙洪帅, 朱华, 高海燕, 万广财, 于秀艳. 肿瘤标志物SCC-Ag、CEA、CYFRA21-1和D-二聚体联合检测对非小细胞肺癌的早期诊断价值[J]. 吉林大学学报(医学版), 2018, 44(05): 1020-1024.
[6]	魏佳, 王瑶琪, 孙旭, 逄仁柱, 杨帅, 石亮, 李勇, 孟宪瑛. 甲状腺癌相关基因及其在临床诊断中应用的研究进展[J]. 吉林大学学报(医学版), 2018, 44(04): 880-885.
[7]	董洁, 王旭, 崔久嵬. DNA损伤修复通路基因多态性与铂类药物治疗非小细胞肺癌敏感性及预后关系的研究进展[J]. 吉林大学学报(医学版), 2018, 44(04): 869-874.
[8]	李晓, 邱香, 马振卉, 田亚萍. 皮肤转移癌伴发带状疱疹1例报告并文献复习[J]. 吉林大学学报(医学版), 2018, 44(04): 825-827.
[9]	王淼, 母润红, 李明成, 李洪杰. RNAi沉默survivin和HIF-1α基因对胃癌BGC-823细胞体外增殖和凋亡的影响[J]. 吉林大学学报(医学版), 2018, 44(04): 753-758.
[10]	严齐会, 朱慧勇. 转录因子KLFs家族与口腔鳞状细胞癌关系的研究进展[J]. 吉林大学学报(医学版), 2018, 44(03): 679-683.
[11]	赵艳杰, 宋清坤, 李军, 何永明, 曲宸绪. 食管鳞状细胞癌高发区人群食用腌肉与食管鳞状细胞癌风险的关系[J]. 吉林大学学报(医学版), 2018, 44(03): 656-660.
[12]	杨文延, 刘强, 孙志娟, 杜利清, 徐畅, 王彦, 柳杨, 王芹. 褪黑素对人非小细胞肺癌H1299细胞辐射敏感性的影响[J]. 吉林大学学报(医学版), 2018, 44(03): 532-536.
[13]	全晓月, 刘百龙, 刘敏, 董丽华. 阿帕替尼治疗无法耐受化疗的肺鳞状细胞癌1例报告及文献复习[J]. 吉林大学学报(医学版), 2018, 44(03): 624-627.
[14]	李波, 刘可可, 段浩博, 王远萍, 唐思嘉, 周乐, 孙宏晨. 肿瘤相关巨噬细胞在口腔鳞状细胞癌发生发展中作用及其靶向治疗的研究进展[J]. 吉林大学学报(医学版), 2018, 44(03): 684-688.
[15]	刘霞, 齐凤杰, 杜晓媛. 沉默CRAF基因表达对肝癌细胞侵袭和迁移的影响[J]. 吉林大学学报(医学版), 2018, 44(03): 521-525.