
浏览全部资源
扫码关注微信
1.330000 南昌, 南昌大学第二附属医院:消化内科
2.330000 南昌, 南昌大学第二附属医院:核医学科
[陈新, E-mail:13870979404@163.com CHEN Xin, 13870979404@163.com
收稿:2021-01-18,
修回:2021-05-06,
纸质出版:2021-09-30
移动端阅览
章诺贝, 沈浩, 黄神安, 等. LncRNA SNHG12通过miR-129-5p/GTPBP4对肝细胞癌进展的促进作用[J]. 第三军医大学学报, 2021,43(18):1783-1795.
Nuobei ZHANG, Hao SHEN, Shen'an HUANG, et al. Long non-coding RNA SNHG12 promotes progression of hepatocellular carcinoma through miR-129-5p/GTPBP4[J]. Journal of Third Military Medical University, 2021, 43(18): 1783-1795.
章诺贝, 沈浩, 黄神安, 等. LncRNA SNHG12通过miR-129-5p/GTPBP4对肝细胞癌进展的促进作用[J]. 第三军医大学学报, 2021,43(18):1783-1795. DOI: 10.16016/j.1000-5404.202101151.
Nuobei ZHANG, Hao SHEN, Shen'an HUANG, et al. Long non-coding RNA SNHG12 promotes progression of hepatocellular carcinoma through miR-129-5p/GTPBP4[J]. Journal of Third Military Medical University, 2021, 43(18): 1783-1795. DOI: 10.16016/j.1000-5404.202101151.
目的
2
探讨长链非编码RNA(LncRNA)核仁小RNA宿主基因12(small nucleolar RNA host gene 12
SNHG12)对肝细胞癌(hepatocellular carcinoma,HCC)发展的调控机制。
方法
2
通过RT-qPCR检测长链非编码RNA(long noncoding RNA,LncRNA) SNHG12在肝癌组织和肝癌细胞系中的表达水平;分析肝癌组织中LncRNA SNHG12的表达水平与HCC患者临床病理参数的关系;运用MTT实验、细胞集落形成实验、Transwell实验、划痕愈合实验、裸鼠成瘤实验检测LncRNA SNHG12、miR-129-5p、GTPBP4在肝癌细胞活性、增殖、迁移、侵袭中的作用;采用荧光素酶报告基因、RT-qPCR、Western blot实验来评估LncRNA SNHG12、miR-129-5p、GTPBP4之间的互相作用。
结果
2
LncRNA SNHG12在肝癌组织和肝癌细胞系中表达上调(
P
<
0.05);LncRNA SNHG12表达水平较高的HCC患者相比其表达水平较低的患者预后更差(
P
<
0.05);LncRNA SNHG12表达水平与肿瘤大小、TNM分期、淋巴结转移存在正相关的关系;LncRNA SNHG12可促进HCC的细胞活性、增殖、迁移及侵袭(
P
<
0.05);miR-129-5p在肝癌组织中表达下调,其可抑制肝癌细胞活性、增殖、迁移及侵袭(
P
<
0.05);LncRNA SNHG12可通过与miR-129-5p进行竞争性结合,从而促进GTPBP4的表达(
P
<
0.05);GTPBP4在HCC组织中表达上调,其可促进肝癌细胞活性、增殖、迁移及侵袭(
P
<
0.05)。
结论
2
LncRNA SNHG12可通过调控miR-129-5p/GTPBP4轴从而促进HCC的进展。
Objective
2
To explore the regulatory mechanism of long non-coding RNA (LncRNA) small nucleolar RNA host gene 12 (SNHG12) on the development of hepatocellular carcinoma (HCC).
Methods
2
The expression levels of SNHG12 in HCC tissues as well as in HCC cell lines were detected by RT-qPCR
and the correlation between the SNHG12 level and the clinicopathological parameters of HCC patients was then analyzed. The effects of SNHG12
miR-129-5p and GTPBP4 on the activity
proliferation
migration and invasion of HCC cells were determined using MTT assay
cell colony formation test
Transwell test
scratch healing assay and xenograft tumor growth assay
respectively. Finally
luciferase reporter gene
RT-qPCR and Western blotting were employed to evaluate the interactions among SNHG12
miR-129-5p and GTPBP4.
Results
2
The expression of SNHG12 was up-regulated in both HCC tissues and HCC cell lines (
P
<
0.05). HCC patients with higher expression level of SNHG12 had a worse prognosis than those with lower level (
P
<
0.05)
and its level was positively correlated with tumor size
TNM stage and lymph node metastasis. LncRNA SNHG12 promoted the viability
proliferation
migration and invasion of HCC cells (
P
<
0.05)
whereas
miR-129-5p was down-regulated in HCC tissues and showed inhibitory effects on above biological behaviors of HCC cells (
P
<
0.05). Moreover
through competitively binding with miR-129-5p
SNHG12 promoted GTPBP4 expression (
P
<
0.05)
which was up-regulated in HCC tissues and facilitated the activity
proliferation
migration and invasion of HCC cells (
P
<
0.05).
Conclusion
2
LncRNA SNHG12 promotes the progression of HCC by regulating the miR-129-5p/GTPBP4 axis.
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.
PINATO D J, GUERRA N, FESSAS P, et al . Immune-based therapies for hepatocellular carcinoma[J ] . Oncogene, 2020, 39(18): 3620-3637. DOI: 10.1038/s41388-020-1249-9.
GOODALL G J, WICKRAMASINGHE V O. RNA in cancer[J]. Nat Rev Cancer, 2021, 21(1): 22-36. DOI: 10.1038/s41568-020-00306-0.
HUANG Z, ZHOU J K, PENG Y, et al . The role of long noncoding RNAs in hepatocellular carcinoma[J ] . Mol Cancer, 2020, 19(1): 77. DOI: 10.1186/s12943-020-01188-4.
LI Z R, YANG Q, ZHOU T, et al . Prognostic value of long noncoding RNA SNHG12 in various carcinomas: A meta-analysis[J ] . Biomed Res Int, 2020, 2020: 8847401. DOI: 10.1155/2020/8847401.eCollection2020.
LIU Y, CHENG G, HUANG Z, et al . Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma[J ] . Cell Death Dis, 2020, 8;11(7): 515. DOI: 10.1038/s41419-020-2713-8.
WANG C, SHAO S, DENG L, et al . LncRNA SNHG12 regulates the radiosensitivity of cervical cancer through the miR-148a/CDK1 pathway[J ] . Cancer Cell Int, 2020, 20(1): 554. DOI: 10.1186/s12935-020-01654-5.
ZHANG C, REN X, ZHANG W, et al . Prognostic and clinical significance of long non-coding RNA SNHG12 expression in various cancers[J ] . Bioengineered, 2020, 11(1): 1112-1123. DOI: 10.1080/21655979.2020.1831361.
ZHANG J J, LOU W Y. A key mRNA-miRNA-lncRNA competing endogenous RNA triple sub-network linked to diagnosis and prognosis of hepatocellular carcinoma[J]. Front Oncol, 2020, 10: 340. DOI: 10.3389/fonc.2020.00340.
PANNI S, LOVERING R C, PORRAS P, et al . Non-coding RNA regulatory networks[J ] . Biochim Biophys Acta Gene Regul Mech, 2020, 1863(6): 194417. DOI: 10.1016/j.bbagrm.2019.194417.
ZHAO Z, SUN W, GUO Z, et al . Mechanisms of lncRNA/microRNA interactions in angiogenesis[J ] . Life Sci, 2020, 254: 116900. DOI: 10.1016/j.lfs.2019.116900.
WANG P, CHEN D, MA H, et al . LncRNA SNHG12 contributes to multidrug resistance through activating the MAPK/Slug pathway by sponging miR-181a in non-small cell lung cancer[J ] . Oncotarget, 2017, 8(48): 84086-84101. DOI: 10.18632/oncotarget.20475.
LIU Z, SUN J, WANG X, et al . MicroRNA-129-5p promotes proliferation and metastasis of hepatocellular carcinoma by regulating the BMP2 gene[J ] . Exp Ther Med, 2021, 21(3): 257. DOI: 10.3892/etm.2021.9688.
LI Z, LU J, ZENG G, et al . MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase Ⅳ (CAMK4)[J ] . Cell Death Dis, 2019, 10(11): 789. DOI: 10.1038/s41419-019-1923-4.
TAO J, LIU Z, WANG Y, et al . MiR-129-5p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting UBE3C[J ] . Biomed Pharmacother, 2017, 93: 420-428. DOI: 10.1016/j.biopha.2017.06.070.
ZHANG X, XU S, HU C, et al . LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma progression by regulating MAGEA3 and DCAF4L2 expression[J ] . Biochem Biophys Res Commun, 2020, 533(4): 1039-1047. DOI: 10.1016/j.bbrc.2020.09.115.
LI L, PANG X, ZHU Z, et al . GTPBP4 Promotes Gastric Cancer Progression via Regulating P53 Activity[J ] . Cell Physiol Biochem, 2018, 45(2): 667-676. DOI: 10.1159/000487160.
YU H, JIN S, ZHANG N, et al . Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis[J ] . Biochem Biophys Res Commun, 2016, 480(1): 48-54. DOI: 10.1016/j.bbrc.2016.10.010.
LUNARDI A, DI MININ G, PROVERO P, et al . A genome-scale protein interaction profile of Drosophila p53 uncovers additional nodes of the human p53 network[J ] . Proc Natl Acad Sci USA, 2010, 107(14): 6322-6327. DOI: 10.1073/pnas.1002447107.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621