Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

Background: The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin β-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expre...

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Main Authors: Yuta Kurota, Yuji Takeda, Osamu Ichiyanagi, Shinichi Saitoh, Hiromi Ito, Sei Naito, Hironobu Asao, Norihiko Tsuchiya
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/11/5/1330
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author Yuta Kurota
Yuji Takeda
Osamu Ichiyanagi
Shinichi Saitoh
Hiromi Ito
Sei Naito
Hironobu Asao
Norihiko Tsuchiya
author_facet Yuta Kurota
Yuji Takeda
Osamu Ichiyanagi
Shinichi Saitoh
Hiromi Ito
Sei Naito
Hironobu Asao
Norihiko Tsuchiya
author_sort Yuta Kurota
collection DOAJ
description Background: The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin β-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expressed in several carcinomas. However, the relationship between HBB expression and the prognosis of renal cell carcinoma (RCC) remains unclear. Methods: HBB expression was immunohistochemically analyzed in 203 nonmetastatic clear cell RCC (ccRCC) cases. Cell proliferation, invasion, and ROS production were measured in ccRCC cell lines treated with HBB-specific siRNA. Results: The prognosis of HBB-positive patients was worse than that of HBB-negative patients. Cell proliferation and invasion were inhibited, and ROS production was increased by treatment with HBB-specific siRNA. Oxidative stress increased HBB expression in cells exposed to H<sub>2</sub>O<sub>2</sub>. Conclusions: HBB expression in ccRCC contributes to cancer cell proliferation by suppressing ROS production under hypoxic conditions. Taken together with clinical results and in vitro experiments, HBB expression may serve as a new prognostic biomarker for RCC in the future.
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spelling doaj.art-cc0a108a8f5941cf9f08afc9861878ff2023-11-18T00:35:28ZengMDPI AGBiomedicines2227-90592023-04-01115133010.3390/biomedicines11051330Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell CarcinomaYuta Kurota0Yuji Takeda1Osamu Ichiyanagi2Shinichi Saitoh3Hiromi Ito4Sei Naito5Hironobu Asao6Norihiko Tsuchiya7Department of Urology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanDepartment of Immunology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanDepartment of Immunology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanDepartment of Immunology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, 2-2-2, Iida-Nishi, Yamagata 990-9585, JapanBackground: The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin β-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expressed in several carcinomas. However, the relationship between HBB expression and the prognosis of renal cell carcinoma (RCC) remains unclear. Methods: HBB expression was immunohistochemically analyzed in 203 nonmetastatic clear cell RCC (ccRCC) cases. Cell proliferation, invasion, and ROS production were measured in ccRCC cell lines treated with HBB-specific siRNA. Results: The prognosis of HBB-positive patients was worse than that of HBB-negative patients. Cell proliferation and invasion were inhibited, and ROS production was increased by treatment with HBB-specific siRNA. Oxidative stress increased HBB expression in cells exposed to H<sub>2</sub>O<sub>2</sub>. Conclusions: HBB expression in ccRCC contributes to cancer cell proliferation by suppressing ROS production under hypoxic conditions. Taken together with clinical results and in vitro experiments, HBB expression may serve as a new prognostic biomarker for RCC in the future.https://www.mdpi.com/2227-9059/11/5/1330hemoglobin β-chain (HBB)malignant transformationredox balancerenal cell carcinoma (RCC)
spellingShingle Yuta Kurota
Yuji Takeda
Osamu Ichiyanagi
Shinichi Saitoh
Hiromi Ito
Sei Naito
Hironobu Asao
Norihiko Tsuchiya
Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma
Biomedicines
hemoglobin β-chain (HBB)
malignant transformation
redox balance
renal cell carcinoma (RCC)
title Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma
title_full Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma
title_fullStr Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma
title_full_unstemmed Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma
title_short Hemoglobin β Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma
title_sort hemoglobin β expression is associated with poor prognosis in clear cell renal cell carcinoma
topic hemoglobin β-chain (HBB)
malignant transformation
redox balance
renal cell carcinoma (RCC)
url https://www.mdpi.com/2227-9059/11/5/1330
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