miR-146a通过靶向CCNJ调控鼻咽癌细胞HNE-1/DDP对顺铂敏感性的影响

doi:10.13418/j.issn.1001-165x.2021.01.011

中国临床解剖学杂志 ›› 2021, Vol. 39 ›› Issue (1): 55-59.doi: 10.13418/j.issn.1001-165x.2021.01.011

miR-146a通过靶向CCNJ调控鼻咽癌细胞HNE-1/DDP对顺铂敏感性的影响

周兰柱，　赵报，　张明洁，　崔忆旋，　吴俊，　孙哲，　柳申成，　王文忠

蚌埠医学院第一附属医院耳鼻喉头颈外科，安徽蚌埠 233000

收稿日期:2020-01-14 出版日期:2021-01-25 发布日期:2021-01-27
通讯作者: 王文忠，主任医师，硕士生导师，E-mail：13955259093 @163.com
作者简介:周兰柱（1981-），男，安徽蚌埠人，硕士，主治医师，研究方向：头颈部肿瘤，E-mail：20206283@qq.com
基金资助:
国家自然科学基金（81903142）；安徽省高校自然科学研究重点项目（KJ2019A0293，KJ2019A0376）；蚌埠医学院科技发展基金（BYKF1763）；蚌埠医学院自然科学基金重点项目（BYKY1855ZD）

Effect of miR-146a on the sensitivity of nasopharyngeal carcinoma cells HNE-1 / DDP to cisplatin by targeting CCNJ

Zhou Lanzhu, Zhao Bao, Zhang Mingjie, Cui Yixuan, Wu Jun, Sun Zhe, Liu Shencheng, Wang Wenzhong

Department of Otolaryngology, Head and Neck Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui Province, China

Received:2020-01-14 Online:2021-01-25 Published:2021-01-27

摘要/Abstract

摘要： 目的　探讨miR-146a对鼻咽癌耐顺铂细胞HNE-1/DDP顺铂敏感性的作用及可能机制。方法　实验分空白组、阴性对照组及mimics-miR-146a组。MTT检测HNE-1/DDP细胞在不同方法处理后的增殖抑制作用；Annexin V-FITC／PI双染法检测细胞凋亡情况；Western blot检测周期蛋白CCNJ、MRP1、P-gp的相对表达水平；实时荧光定量PCR（RT-qPCR）检测CCNJ mRNA的相对表达水平。结果　与其他两组相比，mimics-miR-146a组存活率降低，凋亡率升高，MRP1、P-gp、CCNJ蛋白表达量降低，CCNJ mRNA的相对表达量降低，差异均有统计学意义（P<0.05）。结论　miR-146a可增加HNE-1/DDP对DDP的敏感性，机制可能是miR-146a抑制CCNJ的表达而调控下游蛋白MRP1、P-gp，降低细胞耐药性。

关键词: 鼻咽癌, 　耐药性, 　微小RNA, 　顺铂, 　细胞周期素蛋白J

Abstract: Objective　To investigate the effect of miR-146a on cisplatin sensitivity of nasopharyngeal carcinoma HNE-1 / DDP cells and its possible mechanism.　Methods　The experiment was divided into three groups: a blank control group, a negative control group and a mimics-miR-146a group. MTT assay was used to detect the proliferation inhibition of cells after different treatments. Annexin V-FITC / PI assay was used to detect apoptosis. Western blot was used to detect the relative expression levels of cyclin CCNJ, MRP1, P-gp. RT-qPCR was used to detect the relative expression level of CCNJ mRNA.　Results Compared with other two groups, the survival rate, the relative protein expression levels of MRP1, P-gp, CCNJ and the relative expression level of CCNJ mRNA of mimics-miR-146a reduced, while the apoptosis rate increased. There were statistical differences in the survival rate, the relative protein expression levels of MRP1, P-gp, CCNJ, the relative expression level of CCNJ mRNA and the apoptosis rate among the three groups (P<0.05).　Conclusions　miR-146a can increase the sensitivity of HNE-1/DDP to DDP which mechanism may be through miR-146a inhibiting the expression of CCNJ to regulate downstream proteins MRP1,P-gp,and then to reduce cell resistance.

Key words: Nasopharyngeal carcinoma, 　Drug resistance, 　Micro RNA, 　Cisplatin, 　Cyclin protein

中图分类号:

R766.3

周兰柱, 赵报, 张明洁, 崔忆旋, 吴俊, 孙哲, 柳申成, 王文忠. miR-146a通过靶向CCNJ调控鼻咽癌细胞HNE-1/DDP对顺铂敏感性的影响[J]. 中国临床解剖学杂志, 2021, 39(1): 55-59.

Zhou Lanzhu, Zhao Bao, Zhang Mingjie, Cui Yixuan, Wu Jun, Sun Zhe, Liu Shencheng, Wang Wenzhong. Effect of miR-146a on the sensitivity of nasopharyngeal carcinoma cells HNE-1 / DDP to cisplatin by targeting CCNJ[J]. Chinese Journal of Clinical Anatomy, 2021, 39(1): 55-59.

参考文献 24

[1]	陈德林. 鼻咽癌流行病学的研究与进展[J].中国肿瘤, 1992, (9): 20-21.
[2]	张亚运. 窄带成像诊断鼻咽癌准确性的系统回顾和Meta分析[D]. 无锡: 江南大学, 2018.
[3]	Mcdermott AL, Dutt SN, Watkinson JC. The aetiology of nasopharyngeal carcinoma[J]. Clin Otolaryngol Allied Sci, 2010, 26(2): 82-92. DOI: 10.1046/j.1365-2273.2001.00449.x.
[4]	Chen QY, Wen YF, Guo L, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma:phase III randomized trial[J]. J Natl Cancer Inst, 2011, 103(23): 1761-1770. DOI: 10.1093/jnci/djr432.
[5]	Ambros V. The functions of animal microRNAs[J]. Nature, 2004, 431(7006): 350-355. DOI: 10.1038/nature02871.
[6]	Dai T, Hu Y, Zheng H. Hypoxia increases expression of CXC chemokine receptor 4 via activation of PI3K/Akt leading to enhanced migration of endothelial progenitor cells[J]. Eur Rev Med Pharmacol Sci, 2017, 21(8): 1820-1827. PMID: 28485797.
[7]	Shi L, Xu ZZ, Wu G, et al. Up-regulation of miR-146a increases the sensitivity of non-small cell lung cancer to DDP by downregulating cyclin J[J]. BMC Cancer, 2017, 17(1): 138. DOI: 10.1186/s12885-017-3132-9.
[8]	Li N, Ma Y, Ma L, et al. MicroRNA-488-3p sensitizes malignant melanoma cells to cisplatin by targeting PRKDC[J]. Cell Biol Int, 2017, 41(6): 622-629. DOI: 10.1002/cbin.10765.
[9]	Cheng RR, Lu CY, Zhang GJ, et al. Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1[J]. Oncol Rep, 2017, 37(4): 2129-2136. DOI: 10.3892/or.2017.5505.
[10]	Wang XH, Tang S, Le SY, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth[J]. PloS One, 2008, 3(7): e2557. DOI: 10.1371/journal.pone.0002557.
[11]	He HL, Jazdzewski K, Li W, et al. The role of microRNA genes in papillary thyroid carcinoma[J]. Proc Natl Acad Sci U S A, 2005, 102(52): 19075-19080. DOI: 10.1073/pnas.0509603102.
[12]	Pacifico F, Crescenzi E, Mellone S, et al. Nuclear factor-κB contributes to anaplastic thyroid carcinomas through up-regulation of miR-146a[J]. J Clin Endocrinol Metab, 2010, 95(3): 1421-1430. DOI:10.1210/jc.2009-1128.
[13]	Bhaumik D, Scott GK, Schokrpur S, et al. Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells[J]. Oncogene, 2008, 27(42): 5643-5647. DOI: 10.1038/onc.2008.171.
[14]	Zheng HL, Ma RQ, Wang QZ, et al. MiR-625-3p promotes cell migration and invasion via inhibition of SCAI in colorectal carcinoma cells[J]. Oncotarget, 2015, 6(29): 27805-27815. DOI: 10.18632/oncotarget.4738.
[15]	邵倩倩, 马莹晔, 李慧, 等. MiR-139-5 p通过靶向CXCR4/PI3 K/Akt信号通路增强鼻咽癌DDP耐药细胞对DDP的敏感性[J]. 中华解剖与临床杂志, 2018, 23(2): 149-154. DOI: 10.3760/cma.j.issn.2095-7041.2018.02.013.
[16]	Liu JY, Chen W, Chen ZZ, et al. The effects of microRNA-98 inhibits cell proliferation and invasion by targeting STAT3 in nasopharyngeal carcinoma[J]. Biomed Pharmacother, 2017, 93: 869-878. DOI: 10.1016/j.biopha.2017.06.094.
[17]	Jiang CY, Wang HT, Zhou L, et al. MicroRNA-212 inhibits the metastasis of nasopharyngeal carcinoma by targeting SOX4:[J]. Oncol Rep, 2017, 38(1): 82-88. DOI: 10.3892/or.2017.5641.
[18]	孟凡磊, 王超, 霍晓川, 等. miR-146a促进动脉粥样硬化斑块形成调控机制研究[J]. 解放军医学院学报, 2014, 35(8): 847-849. DOI: 10.3969/j.issn.2095-5227.2014.08.020.
[19]	王文俏, 刘露, 许馨, 等. miR-146a/b在动脉粥样硬化疾病中的研究进展[J]. 生命科学, 2015, 27(4): 471-476. DOI: CNKI:SUN:SMKX.0.2015-04-008.
[20]	Althoff F, Viktorinová I, Kastl J, et al. Drosophila Cyclin J is a mitotically stable Cdk1 partner without essential functions[J]. Dev Biol, 2009, 333(2): 263-272. DOI: 10.1016/j.ydbio.2009.06.042.
[21]	Kolonin MG, Jr FRL. A role for cyclin J in the rapid nuclear division cycles of early Drosophila embryogenesis[J]. Dev Biol, 2000, 227(2): 661-672. DOI: 10.1006/dbio.2000.9916.
[22]	Venturutti L, Russo RIC, Rivas MA, et al. MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1[J]. Oncogene, 2016, 35(48): 6189-6202. DOI: 10.1038/onc.2016.151.
[23]	Takano N, Hishida M, Inokawa Y, et al. CCNJ detected by triple combination array analysis as a tumor-related gene of hepatocellular carcinoma[J]. Int J Oncol, 2015, 46(5): 1963-1970. DOI: 10.3892/ijo.2015.2892.
[24]	Harvey RC, Mullighan CG, Wang XF, et al. Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome[J]. Blood, 2010, 16(23): 4874-4884. DOI: 10.1182/blood-2009-08-239681.

miR-146a通过靶向CCNJ调控鼻咽癌细胞HNE-1/DDP对顺铂敏感性的影响

Effect of miR-146a on the sensitivity of nasopharyngeal carcinoma cells HNE-1 / DDP to cisplatin by targeting CCNJ

可视化

摘要/Abstract

引用本文

使用本文

参考文献 24

相关文章 4

Metrics

本文评价

推荐阅读 0

[1]	宫凤英, 刘钊汝, 王从容, 范钦, 刘诗雅, 李爱武, 吕英. 阴虚体质对鼻咽癌放疗敏感性的影响及其机制探讨[J]. 中国临床解剖学杂志, 2020, 38(3): 339-342.
[2]	张志谦, 张广星, 彭小东. miR-143-3p 靶向MAPK1对人结肠癌细胞增殖，凋亡和侵袭的调节作用#br#[J]. 中国临床解剖学杂志, 2019, 37(3): 292-298.
[3]	王慧,王丰,吴丽贤,郑鸣. 钙蛋白酶小亚基Capn4在鼻咽癌细胞CNE2中DNA损伤修复的作用[J]. 中国临床解剖学杂志, 2017, 35(3): 291-295.
[4]	林浩然, 杨田福, 杨丽, 梁华锋, 李锐锋. 不同度数鼻内镜观察鼻咽癌放疗后鼻咽结构的分析[J]. 中国临床解剖学杂志, 2014, 32(1): 105-108.