Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway

Abstract Background: Cervical cancer (CC) ranks third in the morbidity and mortality of female cancer around the world. Derlin1 has been found to be overexpressed in several human cancers. However, it is still unclear about its roles in CC. The research aims to explore the relationship between Derl...

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Autores principales:	Li,Ling, Liu,Ming, Zhang,Zhihu, Zhang,Wei, Liu,Naifu, Sheng,Xiugui, Wei,Ping
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2019
Materias:	Derlin 1 Cervical cancer Bcl-2 Bax AKT/mTOR
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100101
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spelling	oai:scielo:S0716-976020190001001012019-10-10Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathwayLi,LingLiu,MingZhang,ZhihuZhang,WeiLiu,NaifuSheng,XiuguiWei,Ping Derlin 1 Cervical cancer Bcl-2 Bax AKT/mTOR Abstract Background: Cervical cancer (CC) ranks third in the morbidity and mortality of female cancer around the world. Derlin1 has been found to be overexpressed in several human cancers. However, it is still unclear about its roles in CC. The research aims to explore the relationship between Derlin1 and CC. Methods: We purchased a human CC tissues microarray, which contained CC tissues and corresponding para-cancerous tissues from 93 patients with primary cervical squamous cell carcinoma. Immunohistochemical staining was used to confirm the expression of Derlin1 in these tissues. And we detected the differential expression of Derlin1 in cervical cancer cell lines and normal cervical epithelial cells (H8). Further, the cervical cancer cell lines SiHa and C33A were used as an in vitro model, which was down-regulated the expression of Derlin1 using siRNA interference technology. The effects of Derlin1 down-regulating in CC cell lines on cell proliferation and migration were detected by CCK8 assay and transwell assay, respectively. The effect of Derlin1 down-regulating on apoptosis was analyzed by flow cytometry, and apoptosis-related proteins were detected using western blotting. In-depth mechanisms were studied using western blotting. In addition, the effects of Derlin1 up-regulating in normal cervical epithelial cells also were exposed. Results: Derlin1 was significantly elevated in CC tissues (81.7%, 76/93), and the expression of Derlin 1 was positively correlated with the tumor size, pathological grade, and lymph node metastasis in CC patients. And Derlin 1 was high expressed in cervical cancer cell lines compared to H8 cells. Knockdown of Derlin 1 in cervical cancer cell lines inhibited cell proliferation and migration. Moreover, knockdown of Derlin 1 induced apoptosis and affected the expression of apoptosis-related proteins, including Bcl-2, Bax, Bim, caspase3 and caspase9. Further experiments showed that AKT/mTOR signal pathway might be involve in this processes that knockdown of Derlin 1 inhibited the expression of p-AKT and p-mTOR. Over-expression of Derlin 1 in H8 cells promoted cell proliferation and migration via up-regulated the expression of p-AKT and p-mTOR. Conclusion: Derlin 1 is an oncogene in CC via AKT/mTOR pathway. It might be a potential therapeutic target for CC.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100101en10.1186/s40659-019-0215-x
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Derlin 1 Cervical cancer Bcl-2 Bax AKT/mTOR
spellingShingle	Derlin 1 Cervical cancer Bcl-2 Bax AKT/mTOR Li,Ling Liu,Ming Zhang,Zhihu Zhang,Wei Liu,Naifu Sheng,Xiugui Wei,Ping Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway
description	Abstract Background: Cervical cancer (CC) ranks third in the morbidity and mortality of female cancer around the world. Derlin1 has been found to be overexpressed in several human cancers. However, it is still unclear about its roles in CC. The research aims to explore the relationship between Derlin1 and CC. Methods: We purchased a human CC tissues microarray, which contained CC tissues and corresponding para-cancerous tissues from 93 patients with primary cervical squamous cell carcinoma. Immunohistochemical staining was used to confirm the expression of Derlin1 in these tissues. And we detected the differential expression of Derlin1 in cervical cancer cell lines and normal cervical epithelial cells (H8). Further, the cervical cancer cell lines SiHa and C33A were used as an in vitro model, which was down-regulated the expression of Derlin1 using siRNA interference technology. The effects of Derlin1 down-regulating in CC cell lines on cell proliferation and migration were detected by CCK8 assay and transwell assay, respectively. The effect of Derlin1 down-regulating on apoptosis was analyzed by flow cytometry, and apoptosis-related proteins were detected using western blotting. In-depth mechanisms were studied using western blotting. In addition, the effects of Derlin1 up-regulating in normal cervical epithelial cells also were exposed. Results: Derlin1 was significantly elevated in CC tissues (81.7%, 76/93), and the expression of Derlin 1 was positively correlated with the tumor size, pathological grade, and lymph node metastasis in CC patients. And Derlin 1 was high expressed in cervical cancer cell lines compared to H8 cells. Knockdown of Derlin 1 in cervical cancer cell lines inhibited cell proliferation and migration. Moreover, knockdown of Derlin 1 induced apoptosis and affected the expression of apoptosis-related proteins, including Bcl-2, Bax, Bim, caspase3 and caspase9. Further experiments showed that AKT/mTOR signal pathway might be involve in this processes that knockdown of Derlin 1 inhibited the expression of p-AKT and p-mTOR. Over-expression of Derlin 1 in H8 cells promoted cell proliferation and migration via up-regulated the expression of p-AKT and p-mTOR. Conclusion: Derlin 1 is an oncogene in CC via AKT/mTOR pathway. It might be a potential therapeutic target for CC.
author	Li,Ling Liu,Ming Zhang,Zhihu Zhang,Wei Liu,Naifu Sheng,Xiugui Wei,Ping
author_facet	Li,Ling Liu,Ming Zhang,Zhihu Zhang,Wei Liu,Naifu Sheng,Xiugui Wei,Ping
author_sort	Li,Ling
title	Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway
title_short	Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway
title_full	Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway
title_fullStr	Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway
title_full_unstemmed	Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway
title_sort	derlin1 functions as an oncogene in cervical cancer via akt/mtor signaling pathway
publisher	Sociedad de Biología de Chile
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100101
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_version_	1718441583190212608

Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway

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