碘-125粒子调控微小RNA-193b-5p抑制胃癌的增殖和侵袭

马振桓; 李震; 周香林; 李国剑; 杨国凯; 万嘉; 杜玲娟; 杨镛

doi:10.12259/j.issn.2095-610X.S20220120

碘-125粒子调控微小RNA-193b-5p抑制胃癌的增殖和侵袭

doi: 10.12259/j.issn.2095-610X.S20220120

马振桓^{1, 2, 3},
李震^{1, 2},
周香林³,
李国剑^{1, 2},
杨国凯^{1, 2},
万嘉^{1, 2},
杜玲娟^{1, 2},
杨镛^{1, 2, ,}

1.
云南大学附属医院普外三科，云南昆明　650021
2.
昆明医科大学第四附属医院普外三科，云南昆明　650500
3.
大理大学临床医学院，云南大理　671003

基金项目: 云南省卫生科技基金资助项目（2017NS137，2018NS0008，2018NS0009）；云南省高层次卫生健康技术人才培养专项基金资助项目（H-2017017）；云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目（2018FE001（-076））

详细信息

作者简介:
马振桓（1969～），男，云南昆明人，医学博士，副主任医师，主要从事肿瘤外科、血管外科临床工作

李震与马振桓对本文有同等贡献

通讯作者:
杨镛，E-mail：yncvs126@126.com

中图分类号: R735.2
计量
- 文章访问数: 4208
- HTML全文浏览量: 2298
- PDF下载量: 31
- 被引次数: 0
出版历程
- 收稿日期: 2021-12-27
- 网络出版日期: 2021-12-20
- 刊出日期: 2022-01-15

Iodine-125 Seed Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating MicroRNA-193b-5p Expression

Zhenhuan MA^{1, 2, 3},
Zhen LI^{1, 2},
Xianglin ZHOU³,
Guojian LI^{1, 2},
Guokai YANG^{1, 2},
Jia WAN^{1, 2},
Lingjuan DU^{1, 2},
Yong YANG^{1, 2
, ,}

1.
The 3rd Department. of General Surgery，The Affiliated Hospital of Yunnan University，Kunming Yunnan 650021
2.
The 3rd Department of General Surgery，The 4th Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650021
3.
Clinical Medical College，Dali University，Dali Yunnan 671003，China

摘要

摘要: 目的探究碘-125粒子放疗胃癌过程中微小RNA（miR）-193b-5p的作用。方法以胃癌细胞系BGC-823作为对象，建立碘-125粒子体外照射模型，采用小分子RNA测序技术检测miRNA的表达谱。通过实时定量PCR检测碘-125辐照组和非辐照组细胞中miR-193b-5p的表达水平，使用hsa-miR-193b-5p抑制物和相应阴性抑制物转染胃癌细胞系BGC-823建立miR-193b-5p敲减细胞和对照细胞（miR-193b-5p敲减组和对照组），采用噻唑蓝（MTT）检测2组细胞增殖情况，采用Transwell分析2组细胞的侵袭情况。结果碘-125辐照组细胞miR-193b-5p表达水平（0.853±0.180）显著高于非辐照组（0.173±0.045），差异有统计学意义（t = 6.371，P < 0.05）；敲减组细胞miR-193b-5p表达水平（1.264±0.311）明显低于对照组（12.219±2.464），差异有统计学意义（t = -7.640，P < 0.05）；miR-193b-5p敲减组细胞的增殖能力（0.574±0.382）明显高于对照组细胞（0.424±0.246），差异有统计学意义（t=3.927，P < 0.05）；miR-193b-5p敲减组细胞侵袭数量（222±23）明显高于对照组细胞侵袭数（40±7），差异有统计学意义（t = -13.293，P < 0.05）。结论碘-125放疗胃癌过程中，能通过调控miR-193b-5p的表达抑制胃癌细胞的增殖和侵袭。
- 碘-125粒子 /
- 胃癌 /
- 微小RNA-193b-5p /
- 细胞增殖 /
- 细胞侵袭
Abstract: Objective To investigate the role of microRNA （miRNA, miR）-193b-5p in the process of iodine-125 particle radiotherapy for gastric cancer. Methods Gastric cancer cell line BGC-823 was used as the research object and iodine-125 seed in vitro irradiation model was established, and the expression profile of miRNA was detected by small molecule RNA sequencing. The expression of miR-193b-5p was analyzed by quantitative real time polymerase chain reaction （RT-qPCR）. MiR-193b-5p knockdown cell and control cell lines （knockdown group and control group） were established in gastric cancer cell line BGC-823 by hsa-miR-193b-5p inhibitor and NC inhibitor. Cell proliferation was analyzed by methyl thiazolyl tetrazolium （MTT） assay in the two groups. Cell invasion was analyzed by Transwell. Result Compared with the expression level of miR-193b-5p in the non-irradiated group （0.173±0.045）, the expression of miR-193b-5p in the iodine-125 irradiated group （0.853±0.180） was significantly increased （t = 6.371, P < 0.05）. Compared with the expression of miR-193b-5p in the control group （12.219±2.464）, the expression of miR-193b-5p in the knockdown group （1.264±0.311） was significantly decreased （t = -7.640, P < 0.05）. Compared with the control group （0.424±0.246）, the proliferation of knockdown group （0.574±0.382）was significantly increased （t = 3.927, P < 0.05）. Compared with the control group （40±7）, the number of cell invasion in the knockdown group （222+23） was significantly increased （t = -13.293, P < 0.05）. Conclusion Iodine-125 seed suppresses the proliferation and invasion of gastric cancer cells by regulating the expression of miR-193b-5p in the process of radiotherapy for gastric cancer.
- Iodine-125 seed /
- Gastric cancer /
- microRNA-193b-5p /
- Cell proliferation /
- Cell invasion

HTML全文

图 1 MTT检测敲低miR-193b-5p对BGC-823细胞增殖的影响

Con：阴性对照组；KD：miR-193b-5p敲减组。

Figure 1. The effect of knocking down miR-193b-5p on the proliferation of BGC-823 cells by MTT method

下载: 全尺寸图片幻灯片

图 2 Transwell实验检测敲低miR-193b-5p对BGC-823细胞侵袭的影响

A：对照组与miR-193b-5p敲减组的细胞侵袭情况（×400）；B：2组侵袭细胞数的t检验。Con：阴性对照组；KD：miR-193b-5p敲减组。与阴性对照组比较，^***P < 0.001。

Figure 2. The effect of knocking down miR-193b-5p on the invasion of BGC-823 cells by transwell experiment

下载: 全尺寸图片幻灯片

表 1 小分子RNA测序差异表达microRNAs结果

Table 1. Differentially expressed microRNAs identified by next generation sequencing

成熟的miRNA	miRNA前体	成熟的RNA序列	差异倍数	P	FDR	调节
hsa-miR-17-5p	hsa-mir-17	CAAAGUGCUUACAGUGCAGGUAG	2.074	0.029	0.630	up
hsa-miR-193b-5p	hsa-mir-193b	CGGGGUUUUGAGGGCGAGAUGA	7.000	0.049	0.630	up
hsa-miR-23b-5p	hsa-mir-23b	UGGGUUCCUGGCAUGCUGAUUU	1.750	0.000	0.000	up
hsa-miR-483-5p	hsa-mir-483	AAGACGGGAGGAAAGAAGGGAG	3.569	0.033	0.630	up
hsa-miR-92a-1-5p	hsa-mir-92a-1	AGGUUGGGAUCGGUUGCAAUGCU	5.600	0.007	0.630	up
hsa-miR-127-3p	hsa-mir-127	UCGGAUCCGUCUGAGCUUGGCU	−2.033	0.036	0.630	down
hsa-miR-1285-3p	hsa-mir-1285-1	UCUGGGCAACAAAGUGAGACCU	−2.000	0.000	0.000	down
hsa-miR-1285-3p	hsa-mir-1285-2	UCUGGGCAACAAAGUGAGACCU	−2.000	0.000	0.000	down
hsa-miR-296-5p	hsa-mir-296	AGGGCCCCCCCUCAAUCCUGU	−2.667	0.038	0.630	down
hsa-miR-421	hsa-mir-421	AUCAACAGACAUUAAUUGGGCGC	−1.750	0.000	0.000	down
hsa-miR-495-3p	hsa-mir-495	AAACAAACAUGGUGCACUUCUU	−7.714	0.034	0.630	down
hsa-miR-548am-3p	hsa-mir-548am	CAAAAACUGCAGUUACUUUUGU	−3.333	0.020	0.630	down

下载: 导出CSV

参考文献(20)

[1]	Sung H,Ferlay J,Siegel R L,et al. Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2021,71(3):209-249. doi: 10.3322/caac.21660
[2]	Song Z,Wu Y,Yang J,et al. Progress in the treatment of advanced gastric cancer[J]. Tumour Biol,2017,39(7):1-7.
[3]	Marin J J,Al-Abdulla R,Lozano E,et al. Mechanisms of resistance to chemotherapy in gastric cancer[J]. Anticancer Agents Med Chem,2016,16(3):318-334. doi: 10.2174/1871520615666150803125121
[4]	Kang M,Youn H G,An J Y,et al. Adjuvant chemotherapy vs surgery alone for pT3N0M0 gastric cancer[J]. Ann Surg Oncol,2021,28(3):1437-1444.
[5]	孙晋虎,李梦. ¹²⁵I放射性粒子植入在口腔颌面部恶性肿瘤治疗中的应用[J]. 口腔医学研究,2019,35(5):415-418.
[6]	罗东,唐能,刘国栋,等. 碘125放射性粒子植入近距离治疗不可切除胰腺癌的现状与进展[J]. 中国普通外科杂志,2017,26(9):1193-1201.
[7]	Ma Z. H,Yang Y,Zou L,et al. 125I seed irradiation induces up-regulation of the genes associated with apoptosis and cell cycle arrest and inhibits growth of gastric cancer xenografts[J]. J Exp Clin Cancer Res,2012,31(1):61. doi: 10.1186/1756-9966-31-61
[8]	Khordadmehr M,Shahbazi R,Sadreddini S,et al. miR-193:A new weapon against cancer[J]. J Cell Physiol,2019,234(10):16861-16872. doi: 10.1002/jcp.28368
[9]	Takabayashi K,Kashiwagi K,Kawata T,et al. Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin[J]. Cancer Biol Ther,2014,15(1):81-88. doi: 10.4161/cbt.26610
[10]	Li C. G,Zhou Z. P,Jia Y. Z,et al. Radioactive (125)I seed implantation for locally advanced pancreatic cancer:A retrospective analysis of 50 cases[J]. World J Clin Cases,2020,8(17):3743-3750. doi: 10.12998/wjcc.v8.i17.3743
[11]	Yang D Y,Lin Y P,Xue C,et al. CT-guided percutaneous implantation of (125)I particles in treatment of early lung cancer[J]. J Thorac Dis,2020,12(10):5996-6009. doi: 10.21037/jtd-20-2666
[12]	Luo M,Chen J,Zhong Z,et al. CT-guided 125I brachytherapy combined with chemotherapy for the treatment of unresectable or locally advanced pancreatic carcinoma[J]. Diagn Interv Radiol,2021,27(1):50-58. doi: 10.5152/dir.2020.19371
[13]	Xue Gang,Feng Yao,Li Jia-Bin. Significance of 125I radioactive seed implantation on growth differentiation factor and programmed death receptor-1 during treatment of oral cancer[J]. World Journal of Clinical Cases,2020,8(5):874-886. doi: 10.12998/wjcc.v8.i5.874
[14]	Ji Z,Jiang Y,Tian S,et al. The effectiveness and prognostic factors of CT-guided radioactive I-125 seed implantation for the treatment of recurrent head and neck cancer after external beam radiation therapy[J]. Int J Radiat Oncol Biol Phys,2019,103(3):638-645. doi: 10.1016/j.ijrobp.2018.10.034
[15]	Xia L,Li F,Qiu J,et al. Oncogenic miR-20b-5p contributes to malignant behaviors of breast cancer stem cells by bidirectionally regulating CCND1 and E2F1[J]. BMC Cancer,2020,20(1):949. doi: 10.1186/s12885-020-07395-y
[16]	Jiang F,Zhang L,Liu Y,et al. Overexpression of miR-331 indicates poor prognosis and promotes progression of breast cancer[J]. Oncol Res Treat,2020,43(9):441-448. doi: 10.1159/000508792
[17]	Feliciano A,Garcia-Mayea Y,Jubierre L,et al. miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness in lung cancer[J]. Cell Death Dis,2017,8(10):e3141. doi: 10.1038/cddis.2017.544
[18]	Xu K,Shi J,Mo D,Y et al. miR-219a-1 inhibits colon cancer cells proliferation and invasion by targeting MEMO1[J]. Cancer Biol Ther,2020,21(12):1163-1170. doi: 10.1080/15384047.2020.1843897
[19]	Yang Y,Ma Z H,Li X G,et al. Iodine-125 irradiation inhibits invasion of gastric cancer cells by reactivating microRNA-181c expression[J]. Oncol Lett,2016,12(4):2789-2795. doi: 10.3892/ol.2016.5033
[20]	Wang L,Zhang Y,Zhao L,et al. MicroRNA-193b inhibits the proliferation,migration and invasion of gastric cancer cells via targeting cyclin D1[J]. Acta Histochem,2016,118(4):323-330. doi: 10.1016/j.acthis.2016.02.001

相关文章(20)

[1]	曾庆彬, 徐蓉, 董文志, 陈志坚, 廖伟然, 龙奎. 锌指转录因子Sall4在胰腺癌中的表达及对细胞侵袭和迁移的影响, 昆明医科大学学报.
[2]	郭小兵, 李晓文, 李恒希, 曹艳, 李坪. miR-212-3p靶向调控NAP1L1抑制胶质瘤细胞增殖、迁移和上皮-间充质转化, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20241104
[3]	邓勇军, 陈倩, 邹建彬, 宫政, 刘焕鹏. ZIC1基因过表达激活P53信号通路抑制胸膜间皮瘤细胞增殖, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240405
[4]	梁彩红, 孟明耀, 李欣欣, 熊晶晶, 李檬, 刘梅, 侯宗柳, 黄永坤. 肠道菌群代谢物脱氧胆酸对人脐带间充质干细胞hUC-MSCs增殖及细胞周期的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230402
[5]	王惠, 曾文珺, 张海萍, 郭瑞威. 钙库操纵型钙通道Orai3分子对冠状动脉血管平滑肌细胞增殖的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230423
[6]	张梁, 王保全, 雷喜锋, 王旭, 柯阳, 张玮. M2巨噬细胞来源的外泌体miR-1246调控胃癌细胞的生长和侵袭, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20230724
[7]	王晓寒, 牟善茂, 郝翠芳, 任琳琳, 王敏, 赵彤. 富血小板血浆促进人子宫内膜间充质干细胞（EnMSCs）增殖的机制, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220126
[8]	袁伟, 孟明耀, 李欣欣, 熊晶晶, 李檬, 曹佳, 刘梅, 侯宗柳, 黄永坤. 内毒素的量效和时效对人脐带间充质干细胞增殖的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220928
[9]	钱石兵, 孟明耀, 于鸿滨, 段开文, 李昌全, 夏志刚. 三七总皂苷对人根尖牙乳头干细胞增殖的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20221018
[10]	殷顺会, 周建忠, 李自良. Tiger17促进口腔黏膜成纤维细胞的增殖和迁移, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210823
[11]	齐崧旭, 邱铖, 陈荣军, 陈展辉, 张万宇, 唐世龙, 曹凡, 李春满, 谢楠. XB130在肝癌组织中的表达及其对细胞侵袭、迁移的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210413
[12]	陈思宇, 付帅, 吴勇. 醋酸棉酚对人舌鳞癌Cal-27细胞侵袭性作用的实验研究, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20201101
[13]	寸红丽, 张大福, 李华秀, 王娜, 张治平, 王关顺. 双源双能CT测量碘含量在T1-3/T4a期胃癌分期诊断的应用, 昆明医科大学学报.
[14]	谢环, 田洁, 黄娅芬. shRNA Twist基因对人绒毛膜癌细胞JEG-3增殖、侵袭和凋亡的影响, 昆明医科大学学报.
[15]	胡正雄. TGF-β2和geneX对BrdU标记骨髓间充质干细胞增殖与成骨分化的作用, 昆明医科大学学报.
[16]	袁勇. 适度低氧微环境对体外培养脑胶质瘤干细胞生长的影响, 昆明医科大学学报.
[17]	张健. 盐霉素对人骨肉瘤MG-63细胞体外增殖和凋亡的影响, 昆明医科大学学报.
[18]	宋吉. Cyclin D1、P16及CDK4基因与胃癌相关性的研究进展, 昆明医科大学学报.
[19]	赵瑜敏. 牙龈卟啉单胞菌对兔血管平滑肌细胞增殖和迁移的影响, 昆明医科大学学报.
[20]	. TRB3在同型半胱氨酸抑制内皮细胞增殖中的作用研究, 昆明医科大学学报.