Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation

Gleason Score (GS) 3 + 4 prostate cancer (PCa) is heterogeneous in clinical course and molecular features. Risk stratification of indolent and aggressive PCa with GS 3 + 4 is critical, especially those with bone metastasis (BM) potential. Microarray-based microRNA(miRNA) profiling with eight PCa cas...

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Main Authors: Hongwei Guo, Jinlong Zhao, Xinjun Li, Feifei Sun, Yiming Qin, Xiaorong Yang, Xueting Xiong, Qianshuo Yin, Xueli Wang, Lin Gao, Meng Jiao, Jing Hu, Bo Han
Format: Article
Language:English
Published: Elsevier 2023-04-01
Series:Molecular and Cellular Probes
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Online Access:http://www.sciencedirect.com/science/article/pii/S0890850823000105
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author Hongwei Guo
Jinlong Zhao
Xinjun Li
Feifei Sun
Yiming Qin
Xiaorong Yang
Xueting Xiong
Qianshuo Yin
Xueli Wang
Lin Gao
Meng Jiao
Jing Hu
Bo Han
author_facet Hongwei Guo
Jinlong Zhao
Xinjun Li
Feifei Sun
Yiming Qin
Xiaorong Yang
Xueting Xiong
Qianshuo Yin
Xueli Wang
Lin Gao
Meng Jiao
Jing Hu
Bo Han
author_sort Hongwei Guo
collection DOAJ
description Gleason Score (GS) 3 + 4 prostate cancer (PCa) is heterogeneous in clinical course and molecular features. Risk stratification of indolent and aggressive PCa with GS 3 + 4 is critical, especially those with bone metastasis (BM) potential. Microarray-based microRNA(miRNA) profiling with eight PCa cases with or without BM was used to screen the candidate miRNAs associated with BM. Transwell and MTS assays were used to characterize the function of miRNAs and target gene LASP1. RT-qPCR and immunohistochemistry assays were utilized to illustrate the clinical significance of miRNAs and target gene in a cohort of 309 Chinese PCa cases. In the current study, we identified that miR-1-3p, miR-143–3p and miR-145–5p are associated with BM of GS 3 + 4 PCa. Through functional experiments, we show that miR-1-3p/143–3p/145–5p promotes proliferation and migration of PCa in vitro. LASP1 was predicted as the common target of these three miRNAs which was further confirmed by a luciferase assay. Overexpression of LASP1 was correlated with higher GS, higher pathological stage, and the presence of metastasis by immunohistochemistry. siRNA knockdown of LASP1 significantly suppressed proliferation and migration, whereas overexpression of LASP1 promoted it. Bioinformatics analysis revealed the involvement of Wnt signaling pathway in LASP1 mediated function. LASP1 may activate Wnt signaling by interacting with β-catenin. In all, we suggest that miR-1-3p/143–3p/145–5p are associated with BM of Gleason 3 + 4 PCa. LASP1 is the common target of these miRNAs and may active Wnt signaling by interacting with β-catenin.
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spelling doaj.art-f99afc13ddef472cb573b12773dd16282023-07-04T05:09:09ZengElsevierMolecular and Cellular Probes0890-85082023-04-0168101901Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulationHongwei Guo0Jinlong Zhao1Xinjun Li2Feifei Sun3Yiming Qin4Xiaorong Yang5Xueting Xiong6Qianshuo Yin7Xueli Wang8Lin Gao9Meng Jiao10Jing Hu11Bo Han12The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China; Department of Pathology, Linyi People's Hospital, Linyi, 276000, ChinaDepartment of Thoracic Surgery, Linyi People's Hospital, Linyi, 276000, ChinaDepartment of Pathology, Binzhou People's Hospital, Binzhou, 256610, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, ChinaCollege of Chemical Engineering and Materials Science, Shandong Normal University, 250014, Jinan, ChinaClinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, 250012, ChinaDepartment of Molecular Genetics, University of Toronto, Toronto, Ontario, CanadaSchool of Basic Medical Sciences, Shandong University, Jinan, 250012, ChinaDepartment of Pathology, Binzhou City Central Hospital, Binzhou, 256603, ChinaThe Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, ChinaDepartment of Pathology, The Second Hospital of Shandong University, Jinan, 250033, ChinaDepartment of Pathology, Qilu Hospital of Shandong University, Jinan, 250012, China; Corresponding author. Department of Pathology, Shandong University Qilu Hospital, Jinan, 250012, China.The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China; Department of Pathology, Qilu Hospital of Shandong University, Jinan, 250012, China; Corresponding author. The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, Shandong University, School of Basic Medical Sciences, Jinan, 250012, China.Gleason Score (GS) 3 + 4 prostate cancer (PCa) is heterogeneous in clinical course and molecular features. Risk stratification of indolent and aggressive PCa with GS 3 + 4 is critical, especially those with bone metastasis (BM) potential. Microarray-based microRNA(miRNA) profiling with eight PCa cases with or without BM was used to screen the candidate miRNAs associated with BM. Transwell and MTS assays were used to characterize the function of miRNAs and target gene LASP1. RT-qPCR and immunohistochemistry assays were utilized to illustrate the clinical significance of miRNAs and target gene in a cohort of 309 Chinese PCa cases. In the current study, we identified that miR-1-3p, miR-143–3p and miR-145–5p are associated with BM of GS 3 + 4 PCa. Through functional experiments, we show that miR-1-3p/143–3p/145–5p promotes proliferation and migration of PCa in vitro. LASP1 was predicted as the common target of these three miRNAs which was further confirmed by a luciferase assay. Overexpression of LASP1 was correlated with higher GS, higher pathological stage, and the presence of metastasis by immunohistochemistry. siRNA knockdown of LASP1 significantly suppressed proliferation and migration, whereas overexpression of LASP1 promoted it. Bioinformatics analysis revealed the involvement of Wnt signaling pathway in LASP1 mediated function. LASP1 may activate Wnt signaling by interacting with β-catenin. In all, we suggest that miR-1-3p/143–3p/145–5p are associated with BM of Gleason 3 + 4 PCa. LASP1 is the common target of these miRNAs and may active Wnt signaling by interacting with β-catenin.http://www.sciencedirect.com/science/article/pii/S0890850823000105Gleason score 3+4Risk stratificationMetastasismiRNAsLASP1
spellingShingle Hongwei Guo
Jinlong Zhao
Xinjun Li
Feifei Sun
Yiming Qin
Xiaorong Yang
Xueting Xiong
Qianshuo Yin
Xueli Wang
Lin Gao
Meng Jiao
Jing Hu
Bo Han
Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation
Molecular and Cellular Probes
Gleason score 3+4
Risk stratification
Metastasis
miRNAs
LASP1
title Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation
title_full Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation
title_fullStr Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation
title_full_unstemmed Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation
title_short Identification of miR-1-3p, miR-143–3p and miR-145–5p association with bone metastasis of Gleason 3+4 prostate cancer and involvement of LASP1 regulation
title_sort identification of mir 1 3p mir 143 3p and mir 145 5p association with bone metastasis of gleason 3 4 prostate cancer and involvement of lasp1 regulation
topic Gleason score 3+4
Risk stratification
Metastasis
miRNAs
LASP1
url http://www.sciencedirect.com/science/article/pii/S0890850823000105
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