LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway

Abstract Background Hepatocellular carcinoma (HCC) is now the second leading cause of cancer death worldwide and lacks effectual therapy due to its high rate of tumor recurrence and metastasis. The aim of this study was to investigate the effects of L antigen family member 3 (LAGE3, a member of the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ying Xing, Yang Liu, Zhong Qi, Zhengrong Liu, Xin Wang, Hongyi Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hepatocellular carcinoma L antigen family member 3 Malignant phenotypes JNK and ERK signaling pathway Cytology QH573-671
Acceso en línea:	https://doaj.org/article/83e2192553cf4f549b4f70254deaec85
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:83e2192553cf4f549b4f70254deaec85
record_format	dspace
spelling	oai:doaj.org-article:83e2192553cf4f549b4f70254deaec852021-11-28T12:08:08ZLAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway10.1186/s11658-021-00295-41425-81531689-1392https://doaj.org/article/83e2192553cf4f549b4f70254deaec852021-11-01T00:00:00Zhttps://doi.org/10.1186/s11658-021-00295-4https://doaj.org/toc/1425-8153https://doaj.org/toc/1689-1392Abstract Background Hepatocellular carcinoma (HCC) is now the second leading cause of cancer death worldwide and lacks effectual therapy due to its high rate of tumor recurrence and metastasis. The aim of this study was to investigate the effects of L antigen family member 3 (LAGE3, a member of the LAGE gene family involved in positive transcription) on the progression of HCC. Methods The expression of LAGE3 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, EdU, and cell cycle analysis assay were employed to evaluate the proliferation of HCC cells. Annexin V-FITC/PI and TUNEL assay were used to assess the apoptosis rate of HCC cells. Wound healing and transwell assay were used to investigate the migration and invasion of HCC cells. A xenograft model of HCC was established with 2 × 106 Hep3B or SK-HEP1 cells to investigate the in vivo effects of LAGE3. Then, the protein levels of LAGE3, p-p38, p-38, c-Jun N-terminal kinase (JNK),p-JNK, extracellular signal-regulated kinase (ERK), and p-ERK were detected by western blot. Results We found that LAGE3 was upregulated in HCC tissues compared to adjacent tissues, and its high expression was correlated with poor overall survival by bioinformatics analysis. Next, we manually regulated the expression of LAGE3 in HCC cells. The knockdown of LAGE3 inhibited the proliferation of HCC cells by arresting the cell cycle in G1 phase. Also the downregulation of LAGE3 inhibited cell migration and invasion and induced apoptosis of HCC cells, while overexpression of LAGE3 promoted the malignant phenotypes of HCC. These results were further confirmed by the in vivo growth of HCC xenografts and the inhibition of apoptosis of HCC tumor cells. Furthermore, we found that LAGE3 exerted cancer-promoting effects by potentiating the JNK and ERK signaling pathway. An ERK inhibitor (10 μM SCH772984) or JNK inhibitor (25 μM SP600125) repressed the upregulated LAGE3-induced proliferation, migration, and invasion of HCC cells. Conclusions LAGE3 enhanced the malignant phenotypes of HCC by promoting the JNK and ERK signaling pathway.Ying XingYang LiuZhong QiZhengrong LiuXin WangHongyi ZhangBMCarticleHepatocellular carcinomaL antigen family member 3Malignant phenotypesJNK and ERK signaling pathwayCytologyQH573-671ENCellular & Molecular Biology Letters, Vol 26, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatocellular carcinoma L antigen family member 3 Malignant phenotypes JNK and ERK signaling pathway Cytology QH573-671
spellingShingle	Hepatocellular carcinoma L antigen family member 3 Malignant phenotypes JNK and ERK signaling pathway Cytology QH573-671 Ying Xing Yang Liu Zhong Qi Zhengrong Liu Xin Wang Hongyi Zhang LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway
description	Abstract Background Hepatocellular carcinoma (HCC) is now the second leading cause of cancer death worldwide and lacks effectual therapy due to its high rate of tumor recurrence and metastasis. The aim of this study was to investigate the effects of L antigen family member 3 (LAGE3, a member of the LAGE gene family involved in positive transcription) on the progression of HCC. Methods The expression of LAGE3 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, EdU, and cell cycle analysis assay were employed to evaluate the proliferation of HCC cells. Annexin V-FITC/PI and TUNEL assay were used to assess the apoptosis rate of HCC cells. Wound healing and transwell assay were used to investigate the migration and invasion of HCC cells. A xenograft model of HCC was established with 2 × 106 Hep3B or SK-HEP1 cells to investigate the in vivo effects of LAGE3. Then, the protein levels of LAGE3, p-p38, p-38, c-Jun N-terminal kinase (JNK),p-JNK, extracellular signal-regulated kinase (ERK), and p-ERK were detected by western blot. Results We found that LAGE3 was upregulated in HCC tissues compared to adjacent tissues, and its high expression was correlated with poor overall survival by bioinformatics analysis. Next, we manually regulated the expression of LAGE3 in HCC cells. The knockdown of LAGE3 inhibited the proliferation of HCC cells by arresting the cell cycle in G1 phase. Also the downregulation of LAGE3 inhibited cell migration and invasion and induced apoptosis of HCC cells, while overexpression of LAGE3 promoted the malignant phenotypes of HCC. These results were further confirmed by the in vivo growth of HCC xenografts and the inhibition of apoptosis of HCC tumor cells. Furthermore, we found that LAGE3 exerted cancer-promoting effects by potentiating the JNK and ERK signaling pathway. An ERK inhibitor (10 μM SCH772984) or JNK inhibitor (25 μM SP600125) repressed the upregulated LAGE3-induced proliferation, migration, and invasion of HCC cells. Conclusions LAGE3 enhanced the malignant phenotypes of HCC by promoting the JNK and ERK signaling pathway.
format	article
author	Ying Xing Yang Liu Zhong Qi Zhengrong Liu Xin Wang Hongyi Zhang
author_facet	Ying Xing Yang Liu Zhong Qi Zhengrong Liu Xin Wang Hongyi Zhang
author_sort	Ying Xing
title	LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway
title_short	LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway
title_full	LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway
title_fullStr	LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway
title_full_unstemmed	LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway
title_sort	lage3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the jnk and erk signaling pathway
publisher	BMC
publishDate	2021
url	https://doaj.org/article/83e2192553cf4f549b4f70254deaec85
work_keys_str_mv	AT yingxing lage3promotedcellproliferationmigrationandinvasionandinhibitedcellapoptosisofhepatocellularcarcinomabyfacilitatingthejnkanderksignalingpathway AT yangliu lage3promotedcellproliferationmigrationandinvasionandinhibitedcellapoptosisofhepatocellularcarcinomabyfacilitatingthejnkanderksignalingpathway AT zhongqi lage3promotedcellproliferationmigrationandinvasionandinhibitedcellapoptosisofhepatocellularcarcinomabyfacilitatingthejnkanderksignalingpathway AT zhengrongliu lage3promotedcellproliferationmigrationandinvasionandinhibitedcellapoptosisofhepatocellularcarcinomabyfacilitatingthejnkanderksignalingpathway AT xinwang lage3promotedcellproliferationmigrationandinvasionandinhibitedcellapoptosisofhepatocellularcarcinomabyfacilitatingthejnkanderksignalingpathway AT hongyizhang lage3promotedcellproliferationmigrationandinvasionandinhibitedcellapoptosisofhepatocellularcarcinomabyfacilitatingthejnkanderksignalingpathway
_version_	1718408208322658304

LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway

Ejemplares similares