浏览全部资源
扫码关注微信
lncRNA LSINCT5靶向结合miR-29c调控乳头状甲状腺癌的增殖迁移
Long non-coding RNA LSINCT5 promotes proliferation and metastasis of papillary thyroid cancer by binding to miR-29c
- 第三军医大学学报 2018年40卷第20期 页码：1851-1857
- 作者机构：
400038 重庆，陆军军医大学(第三军医大学)第一附属医院内分泌科
- 作者简介：
[魏平，E-mail：wp301@sina.com WEI Ping, E-mail:wp301@sina.com
- 基金信息：
DOI：10.16016/j.1000-5404.201807173
中图分类号： R394.13;R730.23;R736.1收稿：2018-07-11，
修回：2018-08-30，
纸质出版：2018-10-30
- 稿件说明：
移动端阅览
匡剑韧, 魏平. lncRNA LSINCT5靶向结合miR-29c调控乳头状甲状腺癌的增殖迁移[J]. 第三军医大学学报, 2018,40(20):1851-1857.
Jianren KUANG, Ping WEI. Long non-coding RNA LSINCT5 promotes proliferation and metastasis of papillary thyroid cancer by binding to miR-29c[J]. Journal of Third Military Medical University, 2018, 40(20): 1851-1857.
匡剑韧, 魏平. lncRNA LSINCT5靶向结合miR-29c调控乳头状甲状腺癌的增殖迁移[J]. 第三军医大学学报, 2018,40(20):1851-1857. DOI： 10.16016/j.1000-5404.201807173.
Jianren KUANG, Ping WEI. Long non-coding RNA LSINCT5 promotes proliferation and metastasis of papillary thyroid cancer by binding to miR-29c[J]. Journal of Third Military Medical University, 2018, 40(20): 1851-1857. DOI： 10.16016/j.1000-5404.201807173.
摘要
目的
2
探讨lncRNA LSINCT5靶向结合miR-29c促乳头状甲状腺癌(papillary thyroid cancer，PTC)增殖和迁移的作用及机制。
方法
2
高通量转录芯片筛选PTC癌组织和癌旁组织差异表达lncRNAs。实时荧光定量PCR(qRT-PCR)检测32例来源于本院的PTC配对癌组织和癌旁组织样本(其中男性18例，女性14例，平均年龄57岁)和PTC细胞系中LSINCT5的表达水平。PTC细胞株TPC-1和KAT-5中转染siNC、siLSINCT5-1、siLSINCT5-2后，CCK-8和Transwell迁移实验测定转染各组的细胞增殖和转移水平。采用双荧光素酶报告基因实验验证LSINCT5与miR-29c的靶向结合。TPC-1细胞中转染Control(空质粒组)、LSINCT5、LSINCT5-Mut以及共转染LSINCT5和miR-29c后，qRT-PCR和Western blot检测ITGB1和E-cadherin表达水平。
结果
2
与配对的癌旁组织相比，LSINCT5在癌组织中表达显著升高(
P
<
0.05)。LSINCT5在PTC细胞系中表达均高于人正常甲状腺细胞HT-ori3，差异有统计学意义(
P
<
0.05)。与转染siNC相比，PTC细胞株TPC-1和KAT-5在转染siLSINCT5-1、siLSINCT5-2后，TPC-1和KAT-5细胞的增殖和迁移能力均显著降低(
P
<
0.05)。双荧光素酶报告基因和RIP证实LSINCT5能够与miR-29c特异性结合。与转染LSINCT5组相比，共转染LSINCT5和miR-29c组中TPC-1细胞增殖和迁移能力均显著降低(
P
<
0.05)，ITGB1 mRNA和蛋白表达水平显著下调(
P
<
0.05)，E-cadherin蛋白表达水平上升。
结论
2
LSINCT5能够发挥miRNAs分子海绵的功能，靶向结合miR-29c而抑制miR-29c-ITGB1轴的抑癌作用，促进PTC的增殖和转移。
Abstract
Objective
2
To evaluate the role of long non-coding RNA (lncRNA) LSINCT5 in promoting the proliferation and metastasis of papillary thyroid cancer (PTC) and explore the mechanism.
Methods
2
lncRNA high-throughput chip was employed to screen the differentially expressed lncRNAs between PTC tissues and the adjacent tissues. qRT-PCR was used to detect the expression level of LSINCT5 in paired PTC tissues and adjacent tissues from 32 patients (including 18 male and 14 female patients with a mean age of 57 years) and in PTC and normal human thyroid cell lines. Human PTC cell lines TPC-1 and KAT-5 were transfected with siLSINCT5-1 and siLSINCT5-2 for knocking down LSINCT5 expression
and the changes in cell proliferation and invasion were analyzed using CCK-8 assay and Transwell analysis. Dual luciferase reporter analysis and RIP were used to detect the interaction between LSINCT5 and miR-29c. The mRNA and protein expressions of ITGB1 and E-cadherin in TPC-1 cells co-transfected with LSINCT5 and miR-29c were detected using qRT-PCR and Western blotting.
Results
2
Compared with the adjacent tissues
PTC tissues showed a significantly increased LSINCT5 expression (
P
<
0.05). LSINCT5 expression was also significantly elevated in PTC cell lines compared to normal human thyroid HT-ori3 cells (
P
<
0.05). Compared with siNC transfection
transfection with siLSINCT5-1 and siLSINCT5-2 for LSINCT5 knockdown significantly suppressed the proliferation and migration of TPC-1 and AKT-5 cells (
P
<
0.05). Dual luciferase reporter and RIP analyses confirmed that LSINCT5 could specifically bind to miR-29c. Compared with LSINCT5 transfection alone
co-transfection with LSINCT5 and mir-29c significantly inhibited the cell proliferation and migration (
P
<
0.05)
lowered ITGB1 mRNA and protein expressions (
P
<
0.05)
and increased E-cadherin protein expression in TPC-1 cells.
Conclusions
2
LSINCT5 plays the role of miRNA molecular sponge
and by competitively binding to miR-29c
LSINCT5 attenuates the tumor-inhibiting effect of miR-29c-ITGB1 axis to promote the proliferation and metastasis of PTC.
关键词
Keywords
references
TORRE L A, BRAY F, SIEGEL R L, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108. DOI: 10.3322/caac.21262.
LI Q, LI H, ZHANG L, et al. Identification of novel long non-coding RNA biomarkers for prognosis prediction of papillary thyroid cancer[J]. Oncotarge, 2017, 8(28): 46136-46144. DOI: 10.18632/oncotarget.17556.
LIYANARACHCHI S, LI W, YAN P, et al. Genome-wide expression screening discloses long noncoding RNAs involved in thyroid carcinogenesis[J]. J Clin Endocrinol Metab, 2016, 101(11): 4005-4013. DOI: 10.1210/jc.2016-1991.
JENDRZEJEWSKI J, THOMAS A, LIYANARACHCHI S, et al. PTCSC3 is involved in papillary thyroid carcinoma development by modulating S100A4 gene expression[J]. J Clin Endocrinol Metab, 2015, 100(10): E1370-E1377. DOI: 10.1210/jc.2015-2247.
WANG C, YAN G, ZHANG Y, et al. Long non-coding RNA MEG3 suppresses migration and invasion of thyroid carcinoma by targeting of Rac1[J]. Neoplasma, 2015, 62(4): 541-549. DOI: 10.4149/neo_2015_065.
WANG Y, GU J, LIN X, et al. lncRNA BANCR promotes EMT in PTC via the Raf/MEK/ERK signaling pathway[J]. Oncol Lett, 2018, 15(4): 5865-5870. DOI: 10.3892/ol.2018.8017.
DING S, QU W, JIAO Y, et al. LncRNA SNHG12 promotes the proliferation and metastasis of papillary thyroid carcinoma cells through regulating wnt/beta-catenin signaling pathway[J]. Cancer Biomark, 2018, 22(2): 217-226. DOI: 10.3233/CBM-170777.
ZHU H, LV Z, AN C, et al. Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma[J]. Sci Rep, 2016, 6: 31969. DOI: 10.1038/srep31969.
JEONG S, LEE J, KIM D, et al. Relationship of focally amplified long noncoding on chromosome 1 (FAL1) lncRNA with E2F transcription factors in thyroid cancer[J]. Medicine, 2016, 95(4): e2592. DOI: 10.1097/MD.0000000000002592.
ZHOU Q, CHEN J, FENG J, et al. Long noncoding RNA PVT1 modulates thyroid cancer cell proliferation by recruiting EZH2 and regulating thyroid-stimulating hormone receptor (TSHR) [J]. Tumour Biol, 2016, 37(3): 3105-3113. DOI: 10.1007/s13277-015-4149-9.
CHEN C, ZHOU L, WANG H, et al. Long noncoding RNA CNALPTC1 promotes cell proliferation and migration of papillary thyroid cancer via sponging miR-30 family[J]. Am J Cancer Res, 2018, 8(1): 192-206.
WANG X, LU X, GENG Z, et al. LncRNA PTCSC3/miR-574-5p governs cell proliferation and migration of papillary thyroid carcinoma via Wnt/beta-catenin signaling[J]. J Cell Biochem, 2017, 118(12): 4745-4752. DOI: 10.1002/jcb.26142.
0
浏览量
0
下载量
0
CSCD
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
