Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours

Abstract Testicular germ cell tumour (TGCT) is the most common cancer in young men in large parts of the world, but the aetiology is mainly unknown. Genome-wide association studies have so far identified about 50 susceptibility loci associated with TGCT, including SPRY4. SPRY4 has shown tumour suppr...

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Autores principales:	Mrinal K. Das, Kari Furu, Herman F. Evensen, Øyvind P. Haugen, Trine B. Haugen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d41275b03b5497daee40d9da1ef87f4
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spelling	oai:doaj.org-article:6d41275b03b5497daee40d9da1ef87f42021-12-02T15:08:28ZKnockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours10.1038/s41598-018-20846-82045-2322https://doaj.org/article/6d41275b03b5497daee40d9da1ef87f42018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20846-8https://doaj.org/toc/2045-2322Abstract Testicular germ cell tumour (TGCT) is the most common cancer in young men in large parts of the world, but the aetiology is mainly unknown. Genome-wide association studies have so far identified about 50 susceptibility loci associated with TGCT, including SPRY4. SPRY4 has shown tumour suppressor activity in several cancer cells, such as lung and prostate, while it was found to act as an oncogene in ovarian cancer. An intronic region within the SPRY4 gene produces a long non-coding RNA, SPRY4-IT1, which has been reported to act as an oncogene in melanoma, breast cancer, and colorectal cancer, and as a tumour suppressor in lung cancer. The roles of SPRY4 and SPRY4-IT1 in TGCT development are yet unknown. We found higher expression levels of SPRY4, both mRNA and protein, and of SPRY4-IT1 in human TGCT than in normal adult testis. Small-interfering RNA (siRNA)-mediated transient knockdown of SPRY4 and SPRY4-IT1 in two TGCT cell lines 833 K and NT2-D1 resulted in decreased cell growth, migration, and invasion. Knockdown of SPRY4 and SPRY4-IT1 also led to a significant reduction in the phosphorylation of Akt. Our findings indicate that SPRY4 and SPRY4-IT1 may act as oncogenes in TGCTs via activation of the PI3K / Akt signalling pathway.Mrinal K. DasKari FuruHerman F. EvensenØyvind P. HaugenTrine B. HaugenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mrinal K. Das Kari Furu Herman F. Evensen Øyvind P. Haugen Trine B. Haugen Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours
description	Abstract Testicular germ cell tumour (TGCT) is the most common cancer in young men in large parts of the world, but the aetiology is mainly unknown. Genome-wide association studies have so far identified about 50 susceptibility loci associated with TGCT, including SPRY4. SPRY4 has shown tumour suppressor activity in several cancer cells, such as lung and prostate, while it was found to act as an oncogene in ovarian cancer. An intronic region within the SPRY4 gene produces a long non-coding RNA, SPRY4-IT1, which has been reported to act as an oncogene in melanoma, breast cancer, and colorectal cancer, and as a tumour suppressor in lung cancer. The roles of SPRY4 and SPRY4-IT1 in TGCT development are yet unknown. We found higher expression levels of SPRY4, both mRNA and protein, and of SPRY4-IT1 in human TGCT than in normal adult testis. Small-interfering RNA (siRNA)-mediated transient knockdown of SPRY4 and SPRY4-IT1 in two TGCT cell lines 833 K and NT2-D1 resulted in decreased cell growth, migration, and invasion. Knockdown of SPRY4 and SPRY4-IT1 also led to a significant reduction in the phosphorylation of Akt. Our findings indicate that SPRY4 and SPRY4-IT1 may act as oncogenes in TGCTs via activation of the PI3K / Akt signalling pathway.
format	article
author	Mrinal K. Das Kari Furu Herman F. Evensen Øyvind P. Haugen Trine B. Haugen
author_facet	Mrinal K. Das Kari Furu Herman F. Evensen Øyvind P. Haugen Trine B. Haugen
author_sort	Mrinal K. Das
title	Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours
title_short	Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours
title_full	Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours
title_fullStr	Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours
title_full_unstemmed	Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours
title_sort	knockdown of spry4 and spry4-it1 inhibits cell growth and phosphorylation of akt in human testicular germ cell tumours
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6d41275b03b5497daee40d9da1ef87f4
work_keys_str_mv	AT mrinalkdas knockdownofspry4andspry4it1inhibitscellgrowthandphosphorylationofaktinhumantesticulargermcelltumours AT karifuru knockdownofspry4andspry4it1inhibitscellgrowthandphosphorylationofaktinhumantesticulargermcelltumours AT hermanfevensen knockdownofspry4andspry4it1inhibitscellgrowthandphosphorylationofaktinhumantesticulargermcelltumours AT øyvindphaugen knockdownofspry4andspry4it1inhibitscellgrowthandphosphorylationofaktinhumantesticulargermcelltumours AT trinebhaugen knockdownofspry4andspry4it1inhibitscellgrowthandphosphorylationofaktinhumantesticulargermcelltumours
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Knockdown of SPRY4 and SPRY4-IT1 inhibits cell growth and phosphorylation of Akt in human testicular germ cell tumours

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