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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2014, Vol. 8 Issue (1) : 106-112     DOI: 10.1007/s11684-014-0307-5
RESEARCH ARTICLE |
Correlation of Twist upregulation and senescence bypass during the progression and metastasis of cervical cancer
Tian Wang, Yan Li, Abidan Tuerhanjiang, Wenwen Wang, Zhangying Wu, Ming Yuan, Shixuan Wang()
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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Abstract  

Cervical carcinoma is associated with high propensity for local invasion and lymph node metastasis. However, the molecular alterations that drive progression and metastasis of cervical cancer remain unclear. Cellular senescence has been proposed as the mechanism that protects an organism against cancer progression and metastasis. In addition, Twist, a basic helix-loop-helix transcription factor, has been suggested as an oncogene because it is overexpressed in many types of human cancer. This gene also exhibits a positive function in regulating invasion and metastasis. In this study, Twist was strongly and positively expressed in normal tissue, squamous cell carcinoma (SCC) IA--IIA, and SCC IIB--IIIB (4.3%, 44%, and 88.9%, respectively). The strong positive expressions of the senescence marker CBX3 were 39.1%, 32%, and 15.6%, respectively. The strong positive expressions of Twist in the SCC groups with or without lymph node metastasis were 80.8% and 50%. For CBX3, such expressions were 7.7% and 29.5%, respectively. Results also showed that the expression of Twist was inversely correlated with that of CBX3. Moreover, the knockdown of Twist with target siRNA in SiHa triggered the induction of the chromatin marker of the cellular senescence CBX3 and senescence-associated β-galactosidase activity. Our results suggested that the expression of Twist increased during the progression and metastasis of cervical cancer. Furthermore, Twist-induced senescence bypass is important in this process.

Keywords cervical cancer      senescence      Twist      CBX3      lymph node metastasis     
Corresponding Authors: Wang Shixuan,Email:sxwang2012@hotmail.com   
Issue Date: 26 April 2014
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-014-0307-5     OR     http://academic.hep.com.cn/fmd/EN/Y2014/V8/I1/106
Fig.1  Immunohistochemistry of Twist and CBX3 in cervical tissue. With the progression and metastasis of cervical cancer, the expression levels of Twist increased and the expression of CBX3 decreased apparently (400× magnification). N, SCC specimens without lymph node metastasis; N, SCC specimens with lymph node metastasis.
Twist expression (%)Total
-++ ++ + +
Normal16 (69.6)6 (26.1)1 (4.3)0 (0)23
SCC IA-IIA0 (0)14 (56.0)10 (40.0)1 (4.0)25
SCC IIB-IIIB0 (0)5 (11.1)33 (73.3)7 (15.6)45
Tab.1  Expression of Twist in normal cervical tissues and SCC
Twist expression (%)Total
-++ ++ + +
LN -0 (0%)16 (36.4%)27 (61.3%)1 (2.3%)44
LN+0 (0%)3 (11.5%)16 (61.6%)7 (26.9%)26
Tab.2  Expression of Twist in SCC with or without lymph node metastasis
CBX3 expression (%)Total
-++ ++ + +
Normal4 (17.4)10 (43.5)5 (21.7)4 (17.4)23
SCC IA-IIA9 (36)8 (32)6 (24)2 (8)25
SCC IIB-IIIB19 (42.2)19 (42.2)6 (13.4)1 (2.2)45
Tab.3  Expression of CBX3 in normal cervical tissues and SCC
CBX3 expression (%)Total
-++ ++ + +
LN-16 (36.4%)15 (34.1%)10 (22.7%)3 (6.8%)44
LN+12 (46.2%)12 (46.1%)2 (7.7%)0 (0%)26
Tab.4  Expression of CBX3 in SCC with or without lymph node metastasis
Fig.2  Validation of the association between Twist and CBX3 in cervical cancer cell line. (A) Validating the efficiency of siTwist in SiHa by real-time PCR. Endogenous Twist was significantly ablated in SiHa/siTwist at the mRNA level. (B) Validating the efficiency of siTwist in SiHa by Western blot. Endogenous Twist was significantly ablated in SiHa/siTwist at the protein level. (C) Transwell migration assay was performed to detect migration. (D) Transwell matrigel invasion assay was conducted to detect invasion. (E) Validating the association between Twist and senescence. The knockdown of Twist in SiHa upregulated the CBX3 expression and triggered SA-β-gal activity.
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