LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis

Background: Studies have shown that long non-coding RNAs (lncRNAs) play essential roles in tumor progression and can affect the response to radiotherapy, including in clear cell renal cell carcinoma (ccRCC). LINC02532 has been found to be upregulated in ccRCC. However, not much is known about this l...

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Autores principales:	Xiaoguang Zhou, Bowen Zeng, Yansheng Li, Haozhou Wang, Xiaodong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	clear cell renal cell carcinoma radioresistance LINC02532 miR-654-5p YY1 Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/ed12e6c538554677ae26ad451a08d075
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spelling	oai:doaj.org-article:ed12e6c538554677ae26ad451a08d0752021-11-25T18:29:25ZLINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis10.3390/molecules262270401420-3049https://doaj.org/article/ed12e6c538554677ae26ad451a08d0752021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/7040https://doaj.org/toc/1420-3049Background: Studies have shown that long non-coding RNAs (lncRNAs) play essential roles in tumor progression and can affect the response to radiotherapy, including in clear cell renal cell carcinoma (ccRCC). LINC02532 has been found to be upregulated in ccRCC. However, not much is known about this lncRNA. Hence, this study aimed to investigate the role of LINC02532 in ccRCC, especially in terms of radioresistance. Methods: Quantitative real-time PCR was used to detect the expression of LINC02532, miR-654-5p, and YY1 in ccRCC cells. Protein levels of YY1, cleaved PARP, and cleaved-Caspase-3 were detected by Western blotting. Cell survival fractions, viability, and apoptosis were determined by clonogenic survival assays, CCK-8 assays, and flow cytometry, respectively. The interplay among LINC02532, miR-654-5p, and YY1 was detected by chromatin immunoprecipitation and dual-luciferase reporter assays. In addition, in vivo xenograft models were established to investigate the effect of LINC02532 on ccRCC radioresistance in 10 nude mice. Results: LINC02532 was highly expressed in ccRCC cells and was upregulated in the cells after irradiation. Moreover, LINC02532 knockdown enhanced cell radiosensitivity both in vitro and in vivo. Furthermore, YY1 activated LINC02532 in ccRCC cells, and LINC02532 acted as a competing endogenous RNA that sponged miR-654-5p to regulate YY1 expression. Rescue experiments indicated that miR-654-5p overexpression or YY1 inhibition recovered ccRCC cell functions that had been previously impaired by LINC02532 overexpression. Conclusions: Our results revealed a positive feedback loop of LINC02532/miR-654-5p/YY1 in regulating the radiosensitivity of ccRCC, suggesting that LINC02532 might be a potential target for ccRCC radiotherapy. This study could serve as a foundation for further research on the role of LINC02532 in ccRCC and other cancers.Xiaoguang ZhouBowen ZengYansheng LiHaozhou WangXiaodong ZhangMDPI AGarticleclear cell renal cell carcinomaradioresistanceLINC02532miR-654-5pYY1Organic chemistryQD241-441ENMolecules, Vol 26, Iss 7040, p 7040 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	clear cell renal cell carcinoma radioresistance LINC02532 miR-654-5p YY1 Organic chemistry QD241-441
spellingShingle	clear cell renal cell carcinoma radioresistance LINC02532 miR-654-5p YY1 Organic chemistry QD241-441 Xiaoguang Zhou Bowen Zeng Yansheng Li Haozhou Wang Xiaodong Zhang LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis
description	Background: Studies have shown that long non-coding RNAs (lncRNAs) play essential roles in tumor progression and can affect the response to radiotherapy, including in clear cell renal cell carcinoma (ccRCC). LINC02532 has been found to be upregulated in ccRCC. However, not much is known about this lncRNA. Hence, this study aimed to investigate the role of LINC02532 in ccRCC, especially in terms of radioresistance. Methods: Quantitative real-time PCR was used to detect the expression of LINC02532, miR-654-5p, and YY1 in ccRCC cells. Protein levels of YY1, cleaved PARP, and cleaved-Caspase-3 were detected by Western blotting. Cell survival fractions, viability, and apoptosis were determined by clonogenic survival assays, CCK-8 assays, and flow cytometry, respectively. The interplay among LINC02532, miR-654-5p, and YY1 was detected by chromatin immunoprecipitation and dual-luciferase reporter assays. In addition, in vivo xenograft models were established to investigate the effect of LINC02532 on ccRCC radioresistance in 10 nude mice. Results: LINC02532 was highly expressed in ccRCC cells and was upregulated in the cells after irradiation. Moreover, LINC02532 knockdown enhanced cell radiosensitivity both in vitro and in vivo. Furthermore, YY1 activated LINC02532 in ccRCC cells, and LINC02532 acted as a competing endogenous RNA that sponged miR-654-5p to regulate YY1 expression. Rescue experiments indicated that miR-654-5p overexpression or YY1 inhibition recovered ccRCC cell functions that had been previously impaired by LINC02532 overexpression. Conclusions: Our results revealed a positive feedback loop of LINC02532/miR-654-5p/YY1 in regulating the radiosensitivity of ccRCC, suggesting that LINC02532 might be a potential target for ccRCC radiotherapy. This study could serve as a foundation for further research on the role of LINC02532 in ccRCC and other cancers.
format	article
author	Xiaoguang Zhou Bowen Zeng Yansheng Li Haozhou Wang Xiaodong Zhang
author_facet	Xiaoguang Zhou Bowen Zeng Yansheng Li Haozhou Wang Xiaodong Zhang
author_sort	Xiaoguang Zhou
title	LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis
title_short	LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis
title_full	LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis
title_fullStr	LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis
title_full_unstemmed	LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis
title_sort	linc02532 contributes to radiosensitivity in clear cell renal cell carcinoma through the mir-654-5p/yy1 axis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ed12e6c538554677ae26ad451a08d075
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LINC02532 Contributes to Radiosensitivity in Clear Cell Renal Cell Carcinoma through the miR-654-5p/YY1 Axis

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