RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells

Background RAS p21 protein activator 4 (RASA4) has been recognised as a Ca2+-promoted Ras–MAPK pathway suppressor that inhibits tumour growth. However, the role of RASA4 in cervical squamous cell carcinoma (CESC) remains unclear. Methods The mRNA levels of RASA4 were analysed using the GEO and GEPIA...

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Autores principales:	Junying Chen, Jinbing Huang, Qiaoqiao Huang, Ji Li, Erling Chen, Wensheng Xu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	rasa4 proliferation hifα cervical squamous cell carcinoma Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/a0e35c4cf3b140ed873982750dbe42ed
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spelling	oai:doaj.org-article:a0e35c4cf3b140ed873982750dbe42ed2021-11-11T14:23:43ZRASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells2165-59792165-598710.1080/21655979.2021.2002499https://doaj.org/article/a0e35c4cf3b140ed873982750dbe42ed2021-11-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2002499https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Background RAS p21 protein activator 4 (RASA4) has been recognised as a Ca2+-promoted Ras–MAPK pathway suppressor that inhibits tumour growth. However, the role of RASA4 in cervical squamous cell carcinoma (CESC) remains unclear. Methods The mRNA levels of RASA4 were analysed using the GEO and GEPIA databases. Kaplan–Meier analysis and ROC analyses were conducted to determine the prognostic and diagnostic values for patients from the TCGA-CSCE cohort. The CCK8 and colony assays were performed to assess the impact of RASA4 ectopic expression and gene inactivation on tumour cell proliferation. In vivo experiments were performed. Luciferase reporter assays and LW6 (a HIFα inhibitor) were employed to verify the regulatory relationship between RASA4 and the HIFa signalling pathway. Results The GEPIA and GEO database analysis demonstrated poorly expressed RASA4 in the CESC tissues relative to that in the noncancerous tissues. Based on the TCGA database, poorly expressed RASA4 signified high prognostic and diagnostic values. Ectopically expressed RASA4 weakened the proliferative potential of HeLa cells, whereas RASA4 genetic inactivation produced the opposite impact in the HeLa and C-33A cells. The promoting effect of RASA4 deficiency on tumourigenesis was also recorded in vivo. Subsequently, RASA4 negatively regulated the HIFα-driven luciferase activities and weakened the expression of survivin. Meanwhile, LW6 treatment abrogated the increased proliferation of HeLa cells, as well as the increased expression of survivin by RASA4 depletion. Conclusion Our findings indicated that RASA4 can inhibit the proliferation of cervical cancer cells by inactivating the HIFα signalling pathway, suggesting novel prospects for targeted therapy against CESC.Junying ChenJinbing HuangQiaoqiao HuangJi LiErling ChenWensheng XuTaylor & Francis Grouparticlerasa4proliferationhifαcervical squamous cell carcinomaBiotechnologyTP248.13-248.65ENBioengineered, Vol 0, Iss 0 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	rasa4 proliferation hifα cervical squamous cell carcinoma Biotechnology TP248.13-248.65
spellingShingle	rasa4 proliferation hifα cervical squamous cell carcinoma Biotechnology TP248.13-248.65 Junying Chen Jinbing Huang Qiaoqiao Huang Ji Li Erling Chen Wensheng Xu RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells
description	Background RAS p21 protein activator 4 (RASA4) has been recognised as a Ca2+-promoted Ras–MAPK pathway suppressor that inhibits tumour growth. However, the role of RASA4 in cervical squamous cell carcinoma (CESC) remains unclear. Methods The mRNA levels of RASA4 were analysed using the GEO and GEPIA databases. Kaplan–Meier analysis and ROC analyses were conducted to determine the prognostic and diagnostic values for patients from the TCGA-CSCE cohort. The CCK8 and colony assays were performed to assess the impact of RASA4 ectopic expression and gene inactivation on tumour cell proliferation. In vivo experiments were performed. Luciferase reporter assays and LW6 (a HIFα inhibitor) were employed to verify the regulatory relationship between RASA4 and the HIFa signalling pathway. Results The GEPIA and GEO database analysis demonstrated poorly expressed RASA4 in the CESC tissues relative to that in the noncancerous tissues. Based on the TCGA database, poorly expressed RASA4 signified high prognostic and diagnostic values. Ectopically expressed RASA4 weakened the proliferative potential of HeLa cells, whereas RASA4 genetic inactivation produced the opposite impact in the HeLa and C-33A cells. The promoting effect of RASA4 deficiency on tumourigenesis was also recorded in vivo. Subsequently, RASA4 negatively regulated the HIFα-driven luciferase activities and weakened the expression of survivin. Meanwhile, LW6 treatment abrogated the increased proliferation of HeLa cells, as well as the increased expression of survivin by RASA4 depletion. Conclusion Our findings indicated that RASA4 can inhibit the proliferation of cervical cancer cells by inactivating the HIFα signalling pathway, suggesting novel prospects for targeted therapy against CESC.
format	article
author	Junying Chen Jinbing Huang Qiaoqiao Huang Ji Li Erling Chen Wensheng Xu
author_facet	Junying Chen Jinbing Huang Qiaoqiao Huang Ji Li Erling Chen Wensheng Xu
author_sort	Junying Chen
title	RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells
title_short	RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells
title_full	RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells
title_fullStr	RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells
title_full_unstemmed	RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells
title_sort	rasa4 inhibits the hifα signalling pathway to suppress proliferation of cervical cancer cells
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/a0e35c4cf3b140ed873982750dbe42ed
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RASA4 inhibits the HIFα signalling pathway to suppress proliferation of cervical cancer cells

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