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Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145

BACKGROUND: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate c...

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Autores principales: Zhang, Dingrong, Fang, Cheng, Li, Haibo, Lu, Chunyuan, Huang, Jiaohong, Pan, Jiancheng, Yang, Zhizhao, Liang, Enli, Liu, Zhifei, Zhou, Xiaodong, Xin, Zhongcheng, Chen, Yegang, Cai, Qiliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261405/
https://www.ncbi.nlm.nih.gov/pubmed/34295718
http://dx.doi.org/10.21037/tau-20-1526
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author Zhang, Dingrong
Fang, Cheng
Li, Haibo
Lu, Chunyuan
Huang, Jiaohong
Pan, Jiancheng
Yang, Zhizhao
Liang, Enli
Liu, Zhifei
Zhou, Xiaodong
Xin, Zhongcheng
Chen, Yegang
Cai, Qiliang
author_facet Zhang, Dingrong
Fang, Cheng
Li, Haibo
Lu, Chunyuan
Huang, Jiaohong
Pan, Jiancheng
Yang, Zhizhao
Liang, Enli
Liu, Zhifei
Zhou, Xiaodong
Xin, Zhongcheng
Chen, Yegang
Cai, Qiliang
author_sort Zhang, Dingrong
collection PubMed
description BACKGROUND: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo. METHODS: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice. RESULTS: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014). CONCLUSIONS: We confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145. The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa.
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spelling pubmed-82614052021-07-21 Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145 Zhang, Dingrong Fang, Cheng Li, Haibo Lu, Chunyuan Huang, Jiaohong Pan, Jiancheng Yang, Zhizhao Liang, Enli Liu, Zhifei Zhou, Xiaodong Xin, Zhongcheng Chen, Yegang Cai, Qiliang Transl Androl Urol Original Article BACKGROUND: The long non-coding (lncRNA) RNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is known to promote tumorigenesis, whereas microRNA-145 (miR-145) plays an antitumor role in several cancers. In this study, we aimed to elucidate the role of MALAT1 and miR-145 in prostate cancer cells and investigate the effect of MALAT1 downregulation on prostate cancer (PCa) cells in vitro in vivo. METHODS: The Cancer Genome Atlas (TCGA) datasets were used to carry out the initial bioinformatics analysis; the findings were then tested in LNCaP and CWR22Rv1 cell lines. Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to evaluate the levels of MALAT1 and miR-145 along with related biomarkers. Furthermore, wound-healing and Transwell assays were performed to test the migratory and invasive abilities of PCa cells. Luciferase reporter assays were used to validate the relationship between MALAT1 and miR-145; their down-stream target genes were also studied. To further substantiate these findings in an animal model, tumor studies including immunofluorescence staining of tissues were carried in nude mice. RESULTS: The expression of MALAT1 was upregulated in both LNCaP cell lines and CWR22Rv1 cell lines (F=2.882, t=13.370, P<0.001; F=2.268, t=15.859, P<0.001). Knockdown of MALAT1 reduced the migratory and invasive capabilities of PCa cells (F=0.017, t=12.212, P<0.001; F=10.723, t=6.016, P=0.002). Using direct binding, MALAT1 suppressed the antitumor function of miR-145, which in turn upregulated transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) via SMAD3 and TGFBR2 (F=2.097, t=5.389, P=0.006; F=1.306, t=4.155, P=0.014). CONCLUSIONS: We confirmed that MALAT1 acts as a competing endogenous RNA (ceRNA) of miR-145. The MALAT1 based regulation of MiR-145-5p-SMAD3/TGFBR2 interactions could be an intriguing molecular pathway for the progression of PCa. AME Publishing Company 2021-06 /pmc/articles/PMC8261405/ /pubmed/34295718 http://dx.doi.org/10.21037/tau-20-1526 Text en 2021 Translational Andrology and Urology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zhang, Dingrong
Fang, Cheng
Li, Haibo
Lu, Chunyuan
Huang, Jiaohong
Pan, Jiancheng
Yang, Zhizhao
Liang, Enli
Liu, Zhifei
Zhou, Xiaodong
Xin, Zhongcheng
Chen, Yegang
Cai, Qiliang
Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145
title Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145
title_full Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145
title_fullStr Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145
title_full_unstemmed Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145
title_short Long ncRNA MALAT1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging miR-145
title_sort long ncrna malat1 promotes cell proliferation, migration, and invasion in prostate cancer via sponging mir-145
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261405/
https://www.ncbi.nlm.nih.gov/pubmed/34295718
http://dx.doi.org/10.21037/tau-20-1526
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