BTg-3对甲状腺滤泡癌细胞增殖、侵袭和迁移及WNT/β-catenin信号通路的影响

doi:10.13481/j.1671-587x.20200620

Abstract

Abstract:

Objective To investigate the expression of B-cell translocation gene-3 （BTg-3） in the thyroid follicular carcinoma tissue and cells and its effects on the proliferation， invasion and migration of thyroid follicular carcinoma cells， and to clarify its possible mechanism on the occurence and development of thyroid follicular carcinoma.

Methods

A total of 80 cases of thyroid follicular carcinoma tissue specimens and 80 cases of thyroid follicular adenoma tissue specimens confirmed by pathology were selected. Immunohistochemistry was used to detect the expressions of BTg-3 in thyroid follicular carcinoma and thyroid follicular adenoma tissues. Western blotting method was used to detect the expression levels of BTg-3 protein in thyroid follicular carcinoma CGTHW-1 cells and thyroid follicular adenoma Nthy-ori cells.The thyroid follicular carcinoma CGTHW-1 cells were randomly divided into blank control group （without transfection）， negative control group（transfected with negative control vector），and BTg-3 over-expression group （transfected with BTg-3 over-expression vector）.Plate clone experiment was used to detect the clone formation rates of the thyroid follicular carcinoma CGTHW-1 cells in various groups；Transwell chamber assay was used to determine the number of invasion and migration cells in various groups；Western blotting method was used to detect the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， Vimentin， epithelial cadherin （E-cadherin）， WNT1， β-catenin， glycogen synthesis kinase 3β （GSK3β），and phosphorylated GSK3β （p-GSK3β） proteins in the thyroid follicular carcinoma CGTHW-1 cells in various groups.

Results

The positive expression rate of BTg-3 in thyroid follicular carcinoma tissue was lower than that in thyroid follicular adenoma tissue （χ² = 62.864， P<0.01）.The expression level of BTg-3 protein in the thyroid follicular carcinoma CGTHW-1 cells was lower than that in thyroid follicular epithelium Nthy-ori cells （t = 34.484， P<0.01）.Compared with blank control group and negative control group， the expression level of BTg-3 protein in the thyroid follicular carcinoma CGTHW-1 cells in BTg-3 over-expression group was increased （P<0.05）；the clone formation rate， number of invation cells and number of migration cells in the thyroid follicular carcinoma CGTHW-1 cells in BTg-3 over-expression group were decreased （P<0.05）；the expression levels of Ki67， PCNA， Vimentin， WNT1， β-catenin， and p-GSK3β proteins in the thyroid follicular carcinoma CGTHW-1 cells in BTg-3 over-expression group were decreased （P<0.05）；the expression level of E-cadherin protein was increased （P<0.05）.

Conclusion

The expression levels of BTg-3 in the thyroid follicular cancinoma tissue and cells are decreased. Over-expression of BTg-3 can inhibit the proliferation， invasion，and migration of thyroid follicular carcinoma cells， and inhibit the activation of WNT / β-catenin signaling pathway.

Key words: BTg-3, thyroid follicular carcinoma, cell proliferation, cell invasion, cell migration, WNT/β-catenin pathway

CLC Number:

R736.1

Jinghai DU,Xin GUO. Effects of BTg-3 on proliferation, invasion, migration and WNT / β-catenin signaling pathway of thyroid follicular carcinoma cells[J].Journal of Jilin University(Medicine Edition), 2020, 46(6): 1234-1240.

Figures/Tables 8

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References 18

1	WEN D， LIAO T， MA B， et al. Downregulation of CSN₆ attenuates papillary thyroid carcinoma progression by reducing Wnt/β-catenin signaling and sensitizes cancer cells to FH535 therapy［J］. Cancer Med， 2018， 7（2）： 285-296.
2	PENG L， LI S， LI Y， et al. Regulation of BTG3 by microRNA-20b-5p in non-small cell lung cancer［J］. Oncol Lett， 2019， 18（1）： 137-144.
3	LI J， CHU Z P， HAN H， et al. Suppression of miR-93-5p inhibits high-risk HPV-positive cervical cancer progression via targeting of BTG3［J］. Hum Cell， 2019， 32（2）： 160-171.
4	杜静海，陈春悠，郭欣，等. BTG3在甲状腺乳头状癌组织中的表达及其对细胞增殖、侵袭、迁移的影响［J］. 东南大学学报（医学版）， 2019， 38（6）： 984-988.
5	王向阳，王辉，蔡威，等.迪乔治综合征危象区基因8在胃癌组织的表达及临床意义［J］.中华实验外科杂志，2018，35（2）：341-343.
6	朱新华，曹鹏. 喉鳞状细胞癌组织中USP18、BTG3表达变化及与预后的相关性［J］. 山东医药， 2019， 59（17）： 69-72.
7	LV C， WANG H， TONG Y， et al. The function of BTG3 in colorectal cancer cells and its possible signaling pathway［J］.J Cancer Res Clin Oncol， 2018， 144（2）： 295-308.
8	WEI K， PAN C， YAO G， et al. MiR-106b-5p promotes proliferation and inhibits apoptosis by regulating BTG3 in non-small cell lung cancer［J］. Cell Physiol Biochem， 2017， 44（4）： 1545-1558.
9	LIU L， LIU S， DUAN Q， et al. MicroRNA-142-5p promotes cell growth and migration in renal cell carcinoma by targeting BTG3［J］. Am J Transl Res， 2017， 9（5）： 2394-2402.
10	ZHENG H C， HE H Y， WU J C， et al. The suppressing effects of BTG3 expression on aggressive behaviors and phenotypes of colorectal cancer： an in vitro and vivo study［J］. Oncotarget， 2017， 8（11）： 18322-18336.
11	MAO D， LIU A H， WANG Z P， et al. Cucurbitacin B inhibits cell proliferation and induces cell apoptosis in colorectal cancer by modulating methylation status of BTG3［J］. Neoplasma， 2019， 66（4）： 593-602.
12	ZHANG Z， LI X， XIAO Q， et al. MiR-574-5p mediates the cell cycle and apoptosis in thyroid cancer cells via Wnt/β-catenin signaling by repressing the expression of Quaking proteins［J］. Oncol Lett， 2018， 15（4）： 5841-5848.
13	李慧敏，王晓霞，武美丽，等. siRNA靶向NRP-1基因沉默经Wnt、ROS及TGF-β1途径抑制宫颈癌细胞增殖［J］. 中国免疫学杂志， 2018， 34（11）： 1626-1631.
14	CHEN L L， GAO G X， SHEN F X， et al. SDC4 gene silencing favors human papillary thyroid carcinoma cell apoptosis and inhibits epithelial mesenchymal transition via wnt/β-catenin pathway［J］. Mol Cells， 2018， 41（9）： 853-867.
15	CAMESELLE-TEIJEIRO J M， PETEIRO-GONZÁLEZ D， CANEIRO-GÓMEZ J， et al. Cribriform-morular variant of thyroid carcinoma： a neoplasm with distinctive phenotype associated with the activation of the WNT/β-catenin pathway［J］. Mod Pathol， 2018， 31（8）： 1168-1179.
16	LIU L， WU B， CAI H， et al. Tiam1 promotes thyroid carcinoma metastasis by modulating EMT via Wnt/β-catenin signaling［J］. Exp Cell Res， 2018， 362（2）： 532-540.
17	AN Q， ZHOU Y， HAN C， et al. BTG3 overexpression suppresses the proliferation and invasion in epithelial ovarian cancer cell by regulating AKT/GSK3β/β-catenin signaling［J］. Reprod Sci， 2017， 24（10）： 1462-1468.
18	MAO D， QIAO L， LU H， et al. B-cell translocation gene 3 overexpression inhibits proliferation and invasion of colorectal cancer SW480 cells via Wnt/β-catenin signaling pathway［J］. Neoplasma， 2016， 63（5）： 705-716.

Group	Proliferation activity
Group	(t/h) 24	48	72
Blank control	0.48±0.05	0.87±0.08	1.44±0.12
Negative control	0.49±0.06	0.85±0.09	1.45±0.11
BTg-3 over-expression	0.40±0.05^*△	0.63±0.06^*△	0.95±0.09^*△
F	5.942	20.757	49.587
P	0.010	<0.001	<0.001

Group	Clone formation rate（η/%）	Number of invasion cells	Number of migration cells
Blank control	29.64±2.79	215.42±19.46	209.51±15.62
Negative control	31.02±2.84	213.54±20.31	207.84±16.02
BTg-3 over-expression	14.25±2.61^*△	73.24±15.67^*△	84.19±14.32^*△
F	80.310	134.711	153.737
P	<0.01	<0.01	<0.01

Group	Ki67	PCNA	Vimentin	E-cadherin
Blank control	0.87±0.11	0.42±0.06	0.77±0.12	0.23±0.05
Negative control	0.85±0.12	0.41±0.05	0.76±0.13	0.21±0.04
BTg-3 over-expression	0.21±0.06^*△	0.09±0.02^*△	0.45±0.09^*△	0.44±0.07^*△
F	98.326	113.831	17.642	37.878
P	<0.01	<0.01	<0.01	<0.01

Group	WNT1	β-catenin	GSK3β	p-GSK3β
Blank control	0.32±0.08	0.21±0.05	0.31±0.08	0.34±0.07
Negative control	0.35±0.09	0.23±0.06	0.32±0.09	0.35±0.06
BTg-3 over-expression	0.11±0.03^*△	0.08±0.02^*△	0.36±0.08	0.07±0.02^*△
F	23.318	21.431	0.703	59.539
P	<0.01	<0.01	0.508	<0.01

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Effects of BTg-3 on proliferation, invasion, migration and WNT / β-catenin signaling pathway of thyroid follicular carcinoma cells

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