RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression

Abstract Background The rhomboids are a family of multi-transmembrane proteins, many of which have been implicated in facilitating tumor progression. Little is yet known, however, about rhomboid-associated biomarkers in cancers. An analysis of such biomarkers could yield important insights into the...

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Autores principales:	Lei Wang, Xiu-Xiu Liu, Yu-Meng Yang, Yan Wang, Yuan-Yuan Song, Shan Gao, Lu-Yuan Li, Zhi-Song Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Kidney renal clear cell carcinoma Rhomboids RHBDF2 Cancer prognosis PD-L1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/df4bf013587f4ca28b22dcfb633345d9
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spelling	oai:doaj.org-article:df4bf013587f4ca28b22dcfb633345d92021-11-08T11:13:39ZRHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression10.1186/s12935-021-02277-01475-2867https://doaj.org/article/df4bf013587f4ca28b22dcfb633345d92021-11-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02277-0https://doaj.org/toc/1475-2867Abstract Background The rhomboids are a family of multi-transmembrane proteins, many of which have been implicated in facilitating tumor progression. Little is yet known, however, about rhomboid-associated biomarkers in cancers. An analysis of such biomarkers could yield important insights into the role of the rhomboids in cancer pathology. Methods In this study, we carried out the univariate Cox regression analysis and compared gene expression patterns of several rhomboid genes in 30 types of cancers by using The Cancer Genome Atlas (TCGA) database and the methods delineated in Gene Expression Profiling Interactive Analysis (GEPIA). We then used datasets GSE47032, GSE126964, GSE68417 and 75 paired pathological specimens to verify the influences of the rhomboid genes in cancer progression. Moreover, we carried out Weighted Gene Correlation Network Analysis (WGCNA) to investigate gene-related functions and we exploited potential correlations between rhomboid genes expression and immune cell infiltration in cancer tissues. Furthermore, we constructed gene-knockdown cancer cell lines to investigate rhomboid gene functions. Results We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels. Silencing of the RHBDF2 gene in KIRC cell lines leads to significantly diminished cell proliferation and migration; this is in good agreement with the identification of an enhanced presence of a number of cell growth and migration promoting signaling molecules in KIRC tumors. We found that, although high level of RHBDF2 correlated with increased infiltration of lymphocytes in cancer tissues, artificially overexpressed RHBDF2 led to an inhibition of the activity of the infiltrated immune cells through sustaining PD-L1 protein level. Furthermore, we show that RHBDF2 related cell migration and PD-L1 regulation were potentially mediated by EGFR signaling pathway. Conclusions RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression and may serve as a critical prognostic biomarker for the disease.Lei WangXiu-Xiu LiuYu-Meng YangYan WangYuan-Yuan SongShan GaoLu-Yuan LiZhi-Song ZhangBMCarticleKidney renal clear cell carcinomaRhomboidsRHBDF2Cancer prognosisPD-L1Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Kidney renal clear cell carcinoma Rhomboids RHBDF2 Cancer prognosis PD-L1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Kidney renal clear cell carcinoma Rhomboids RHBDF2 Cancer prognosis PD-L1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Lei Wang Xiu-Xiu Liu Yu-Meng Yang Yan Wang Yuan-Yuan Song Shan Gao Lu-Yuan Li Zhi-Song Zhang RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression
description	Abstract Background The rhomboids are a family of multi-transmembrane proteins, many of which have been implicated in facilitating tumor progression. Little is yet known, however, about rhomboid-associated biomarkers in cancers. An analysis of such biomarkers could yield important insights into the role of the rhomboids in cancer pathology. Methods In this study, we carried out the univariate Cox regression analysis and compared gene expression patterns of several rhomboid genes in 30 types of cancers by using The Cancer Genome Atlas (TCGA) database and the methods delineated in Gene Expression Profiling Interactive Analysis (GEPIA). We then used datasets GSE47032, GSE126964, GSE68417 and 75 paired pathological specimens to verify the influences of the rhomboid genes in cancer progression. Moreover, we carried out Weighted Gene Correlation Network Analysis (WGCNA) to investigate gene-related functions and we exploited potential correlations between rhomboid genes expression and immune cell infiltration in cancer tissues. Furthermore, we constructed gene-knockdown cancer cell lines to investigate rhomboid gene functions. Results We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels. Silencing of the RHBDF2 gene in KIRC cell lines leads to significantly diminished cell proliferation and migration; this is in good agreement with the identification of an enhanced presence of a number of cell growth and migration promoting signaling molecules in KIRC tumors. We found that, although high level of RHBDF2 correlated with increased infiltration of lymphocytes in cancer tissues, artificially overexpressed RHBDF2 led to an inhibition of the activity of the infiltrated immune cells through sustaining PD-L1 protein level. Furthermore, we show that RHBDF2 related cell migration and PD-L1 regulation were potentially mediated by EGFR signaling pathway. Conclusions RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression and may serve as a critical prognostic biomarker for the disease.
format	article
author	Lei Wang Xiu-Xiu Liu Yu-Meng Yang Yan Wang Yuan-Yuan Song Shan Gao Lu-Yuan Li Zhi-Song Zhang
author_facet	Lei Wang Xiu-Xiu Liu Yu-Meng Yang Yan Wang Yuan-Yuan Song Shan Gao Lu-Yuan Li Zhi-Song Zhang
author_sort	Lei Wang
title	RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression
title_short	RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression
title_full	RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression
title_fullStr	RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression
title_full_unstemmed	RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression
title_sort	rhbdf2 gene functions are correlated to facilitated renal clear cell carcinoma progression
publisher	BMC
publishDate	2021
url	https://doaj.org/article/df4bf013587f4ca28b22dcfb633345d9
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RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression

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