HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer

The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is assoc...

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Main Authors: Jianming Lu, Chuanfan Zhong, Junqi Luo, Fangpeng Shu, Daojun Lv, Zezhen Liu, Xiao Tan, Shuo Wang, Kaihui Wu, Taowei Yang, Weibo Zhong, Bin Wang, Yanfei Chen, Yuehan Li, Zhenyu Jia, Yaguang Zou, Weide Zhong, Xiangming Mao
Format: Article
Language:English
Published: Elsevier 2021-12-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253121002493
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author Jianming Lu
Chuanfan Zhong
Junqi Luo
Fangpeng Shu
Daojun Lv
Zezhen Liu
Xiao Tan
Shuo Wang
Kaihui Wu
Taowei Yang
Weibo Zhong
Bin Wang
Yanfei Chen
Yuehan Li
Zhenyu Jia
Yaguang Zou
Weide Zhong
Xiangming Mao
author_facet Jianming Lu
Chuanfan Zhong
Junqi Luo
Fangpeng Shu
Daojun Lv
Zezhen Liu
Xiao Tan
Shuo Wang
Kaihui Wu
Taowei Yang
Weibo Zhong
Bin Wang
Yanfei Chen
Yuehan Li
Zhenyu Jia
Yaguang Zou
Weide Zhong
Xiangming Mao
author_sort Jianming Lu
collection DOAJ
description The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is associated with pro-proliferation and anti-apoptosis activities in prostate tumor cells. In this study, we aim to establish the biological relevance of circCSPP1 (a newly discovered signature circRNA in prostate cancer [PCa]) and HnRNP-L to prostate cancer progression. First, we demonstrated that circCSPP1 expression was higher in prostate cancer tissues than in benign tissues and higher in prostate cancer cells than in benign cells. Then, the in vitro gain- and loss-of-function experiments showed that the circCSPP1 expression in prostate cancer cells was regulated by HnRNP-L, and the increased circCSPP1 significantly induced autophagy, which led to an enhanced potential in proliferation, migration, and invasion of prostate cancer cells. These results were consistent with the in vivo experiment where increased or decreased circCSPP1 was associated with higher or slower growth rate in grafted tumors. Finally, we demonstrated the potential competing endogenous RNA network, involving circCSPP1, miR-520h, and early growth response factor 1 (EGR1), in prostate cancer cells, which may play an important role in prostate cancer progression. Our study indicated that the increase in circCSPP1 in prostate cancer, which may be catalyzed by HnRNP-L, can induce cellular autophagy through the circCSPP1-miR-520h-EGR1 axis, leading to the progression of prostate tumor. This newly discovered circRNA biomarker may be used for clinical prognosis of prostate cancer as well as for development of novel therapy plans.
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spelling doaj.art-83707a8c1a534f6abab965e93be541bc2022-12-21T18:02:06ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-12-0126927944HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancerJianming Lu0Chuanfan Zhong1Junqi Luo2Fangpeng Shu3Daojun Lv4Zezhen Liu5Xiao Tan6Shuo Wang7Kaihui Wu8Taowei Yang9Weibo Zhong10Bin Wang11Yanfei Chen12Yuehan Li13Zhenyu Jia14Yaguang Zou15Weide Zhong16Xiangming Mao17Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Minimally Invasive Surgery Center, the First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou 510120, Guangdong, P.R. ChinaDepartment of Urology, Minimally Invasive Surgery Center, the First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou 510120, Guangdong, P.R. ChinaDepartment of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, P.R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. ChinaDepartment of Urology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong 510095, P.R. ChinaDepartment of Urology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou, Guangdong 510095, P.R. ChinaCollege of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA 90089, USADepartment of Botany and Plant Sciences, University of California, Riverside, CA 92521, USADepartment of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, P.R. China; Corresponding author: Yaguang Zou, Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, P.R. China.Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China; Corresponding author: Weide Zhong, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P.R. China.E-mail:Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. China; Corresponding author: Xiangming Mao, Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, P.R. China.The circRNAs, a new subclass of non-coding RNAs that are catalyzed by RNA-binding proteins (RBPs), have been reported to be associated with the progression of multiple types of cancer. We previously discovered that heterogeneous nuclear ribonucleoprotein L (HnRNP-L), a multi-functional RBP, is associated with pro-proliferation and anti-apoptosis activities in prostate tumor cells. In this study, we aim to establish the biological relevance of circCSPP1 (a newly discovered signature circRNA in prostate cancer [PCa]) and HnRNP-L to prostate cancer progression. First, we demonstrated that circCSPP1 expression was higher in prostate cancer tissues than in benign tissues and higher in prostate cancer cells than in benign cells. Then, the in vitro gain- and loss-of-function experiments showed that the circCSPP1 expression in prostate cancer cells was regulated by HnRNP-L, and the increased circCSPP1 significantly induced autophagy, which led to an enhanced potential in proliferation, migration, and invasion of prostate cancer cells. These results were consistent with the in vivo experiment where increased or decreased circCSPP1 was associated with higher or slower growth rate in grafted tumors. Finally, we demonstrated the potential competing endogenous RNA network, involving circCSPP1, miR-520h, and early growth response factor 1 (EGR1), in prostate cancer cells, which may play an important role in prostate cancer progression. Our study indicated that the increase in circCSPP1 in prostate cancer, which may be catalyzed by HnRNP-L, can induce cellular autophagy through the circCSPP1-miR-520h-EGR1 axis, leading to the progression of prostate tumor. This newly discovered circRNA biomarker may be used for clinical prognosis of prostate cancer as well as for development of novel therapy plans.http://www.sciencedirect.com/science/article/pii/S2162253121002493prostate cancerHnRNP-LcircCSPP1microRNA-520hEGR1autophagy
spellingShingle Jianming Lu
Chuanfan Zhong
Junqi Luo
Fangpeng Shu
Daojun Lv
Zezhen Liu
Xiao Tan
Shuo Wang
Kaihui Wu
Taowei Yang
Weibo Zhong
Bin Wang
Yanfei Chen
Yuehan Li
Zhenyu Jia
Yaguang Zou
Weide Zhong
Xiangming Mao
HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer
Molecular Therapy: Nucleic Acids
prostate cancer
HnRNP-L
circCSPP1
microRNA-520h
EGR1
autophagy
title HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer
title_full HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer
title_fullStr HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer
title_full_unstemmed HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer
title_short HnRNP-L-regulated circCSPP1/miR-520h/EGR1 axis modulates autophagy and promotes progression in prostate cancer
title_sort hnrnp l regulated circcspp1 mir 520h egr1 axis modulates autophagy and promotes progression in prostate cancer
topic prostate cancer
HnRNP-L
circCSPP1
microRNA-520h
EGR1
autophagy
url http://www.sciencedirect.com/science/article/pii/S2162253121002493
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