Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer
Background: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess th...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2016-01-01
|
| Series: | Chinese Medical Journal |
| Subjects: | |
| Online Access: | http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=13;spage=1544;epage=1552;aulast=Chu |
| _version_ | 1819238210865201152 |
|---|---|
| author | Bing-Feng Chu Yi-Yu Qin Sheng-Lai Zhang Zhi-Wei Quan Ming-Di Zhang Jian-Wei Bi |
| author_facet | Bing-Feng Chu Yi-Yu Qin Sheng-Lai Zhang Zhi-Wei Quan Ming-Di Zhang Jian-Wei Bi |
| author_sort | Bing-Feng Chu |
| collection | DOAJ |
| description | Background: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer.
Methods: Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan–Meier were used to analyze the differences between two group or three groups.
Results: NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression.
Conclusion: Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy. |
| first_indexed | 2024-12-23T13:32:37Z |
| format | Article |
| id | doaj.art-319279f2c7884d66845604cfe973a501 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 |
| language | English |
| last_indexed | 2024-12-23T13:32:37Z |
| publishDate | 2016-01-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-319279f2c7884d66845604cfe973a5012022-12-21T17:45:06ZengWolters KluwerChinese Medical Journal0366-69992016-01-01129131544155210.4103/0366-6999.184465Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid CancerBing-Feng ChuYi-Yu QinSheng-Lai ZhangZhi-Wei QuanMing-Di ZhangJian-Wei BiBackground: The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Methods: Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan–Meier were used to analyze the differences between two group or three groups. Results: NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Conclusion: Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=13;spage=1544;epage=1552;aulast=ChuApoptosis; Cell Cycle Checkpoints; Notch-regulated Ankyrin Repeat Protein; Thyroid Neoplasms |
| spellingShingle | Bing-Feng Chu Yi-Yu Qin Sheng-Lai Zhang Zhi-Wei Quan Ming-Di Zhang Jian-Wei Bi Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer Chinese Medical Journal Apoptosis; Cell Cycle Checkpoints; Notch-regulated Ankyrin Repeat Protein; Thyroid Neoplasms |
| title | Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer |
| title_full | Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer |
| title_fullStr | Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer |
| title_full_unstemmed | Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer |
| title_short | Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer |
| title_sort | downregulation of notch regulated ankyrin repeat protein exerts antitumor activities against growth of thyroid cancer |
| topic | Apoptosis; Cell Cycle Checkpoints; Notch-regulated Ankyrin Repeat Protein; Thyroid Neoplasms |
| url | http://www.cmj.org/article.asp?issn=0366-6999;year=2016;volume=129;issue=13;spage=1544;epage=1552;aulast=Chu |
| work_keys_str_mv | AT bingfengchu downregulationofnotchregulatedankyrinrepeatproteinexertsantitumoractivitiesagainstgrowthofthyroidcancer AT yiyuqin downregulationofnotchregulatedankyrinrepeatproteinexertsantitumoractivitiesagainstgrowthofthyroidcancer AT shenglaizhang downregulationofnotchregulatedankyrinrepeatproteinexertsantitumoractivitiesagainstgrowthofthyroidcancer AT zhiweiquan downregulationofnotchregulatedankyrinrepeatproteinexertsantitumoractivitiesagainstgrowthofthyroidcancer AT mingdizhang downregulationofnotchregulatedankyrinrepeatproteinexertsantitumoractivitiesagainstgrowthofthyroidcancer AT jianweibi downregulationofnotchregulatedankyrinrepeatproteinexertsantitumoractivitiesagainstgrowthofthyroidcancer |