PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression

Abstract Clear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them...

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Autores principales: Lifeng Ding, Ruyue Wang, Wanjiang Xu, Danyang Shen, Sheng Cheng, Huan Wang, Zeyi Lu, Qiming Zheng, Liya Wang, Liqun Xia, Gonghui Li
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Publicado: Nature Publishing Group 2021
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Acceso en línea:https://doaj.org/article/372c8da8797f4361905ad6a6750c53fd
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spelling oai:doaj.org-article:372c8da8797f4361905ad6a6750c53fd2021-11-07T12:21:23ZPIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression10.1038/s41420-021-00725-42058-7716https://doaj.org/article/372c8da8797f4361905ad6a6750c53fd2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00725-4https://doaj.org/toc/2058-7716Abstract Clear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particularly in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC were selected by using piRNA-sequencing combined with TCGA data analysis, and piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could potentially reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further study revealed that piR-57125 modulated ccRCC metastasis through the AKT/ERK pathway. These data indicate that piR-57125 restrains ccRCC metastasis by directly targeting CCL3 and inhibiting the AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.Lifeng DingRuyue WangWanjiang XuDanyang ShenSheng ChengHuan WangZeyi LuQiming ZhengLiya WangLiqun XiaGonghui LiNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Lifeng Ding
Ruyue Wang
Wanjiang Xu
Danyang Shen
Sheng Cheng
Huan Wang
Zeyi Lu
Qiming Zheng
Liya Wang
Liqun Xia
Gonghui Li
PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression
description Abstract Clear-cell renal cell carcinoma is one of the most common tumors disagnosed, with nearly one third of patients diagnosed with metastatic ccRCC. Although an increasing number of studies has revealed that piwi-interacting RNAs are aberrantly expressed in diverse types of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particularly in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC were selected by using piRNA-sequencing combined with TCGA data analysis, and piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could potentially reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further study revealed that piR-57125 modulated ccRCC metastasis through the AKT/ERK pathway. These data indicate that piR-57125 restrains ccRCC metastasis by directly targeting CCL3 and inhibiting the AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.
format article
author Lifeng Ding
Ruyue Wang
Wanjiang Xu
Danyang Shen
Sheng Cheng
Huan Wang
Zeyi Lu
Qiming Zheng
Liya Wang
Liqun Xia
Gonghui Li
author_facet Lifeng Ding
Ruyue Wang
Wanjiang Xu
Danyang Shen
Sheng Cheng
Huan Wang
Zeyi Lu
Qiming Zheng
Liya Wang
Liqun Xia
Gonghui Li
author_sort Lifeng Ding
title PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression
title_short PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression
title_full PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression
title_fullStr PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression
title_full_unstemmed PIWI-interacting RNA 57125 restrains clear cell renal cell carcinoma metastasis by downregulating CCL3 expression
title_sort piwi-interacting rna 57125 restrains clear cell renal cell carcinoma metastasis by downregulating ccl3 expression
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/372c8da8797f4361905ad6a6750c53fd
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