Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating char...

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Veröffentlicht in:BioMed research international 2020, Vol.2020 (2020), p.1-17
Hauptverfasser: He, Mao-Lin, Gu, Yong-Yao, Huang, Zhi-Guang, Chen, Gang, Cheng, Ji-Wen, Li, Sheng-Hua, Sun, Yu, Yan, Hai-Biao
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container_end_page 17
container_issue 2020
container_start_page 1
container_title BioMed research international
container_volume 2020
creator He, Mao-Lin
Gu, Yong-Yao
Huang, Zhi-Guang
Chen, Gang
Cheng, Ji-Wen
Li, Sheng-Hua
Sun, Yu
Yan, Hai-Biao
description Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.
doi_str_mv 10.1155/2020/6037434
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The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2020/6037434</identifier><identifier>PMID: 33178832</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Adenosine triphosphatase ; Archives &amp; records ; Bone cancer ; Bone Neoplasms - secondary ; Cancer therapies ; Carcinogenesis ; Carcinogenesis - genetics ; CDC2 Protein Kinase - metabolism ; Chromosomes ; Complications and side effects ; Correlation analysis ; Down-Regulation - genetics ; Enrichment ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene Ontology ; Gene Regulatory Networks ; Genes ; Genetic aspects ; Genomes ; Health aspects ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Metastases ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; mRNA ; Network analysis ; Ontology ; p53 Protein ; Pancreatic cancer ; Patient outcomes ; Phospholipid-translocating ATPase ; Phospholipids ; Prognosis ; Prostate cancer ; Prostatic Neoplasms - diagnosis ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - pathology ; Protein expression ; Protein Interaction Maps - genetics ; Proteins ; Reproducibility of Results ; Ribonucleic acid ; Risk factors ; RNA ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; ROC Curve ; Signal transduction ; Statistical analysis ; Statistical methods ; Target acquisition ; Transfection ; Tumorigenesis</subject><ispartof>BioMed research international, 2020, Vol.2020 (2020), p.1-17</ispartof><rights>Copyright © 2020 Yu Sun et al.</rights><rights>COPYRIGHT 2020 John Wiley &amp; Sons, Inc.</rights><rights>Copyright © 2020 Yu Sun et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Yu Sun et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-e83f3e7d50b00cc8f5b70dc468f6907e566c6adf66157460f99d0aa9014aa423</citedby><cites>FETCH-LOGICAL-c499t-e83f3e7d50b00cc8f5b70dc468f6907e566c6adf66157460f99d0aa9014aa423</cites><orcidid>0000-0003-0709-8509 ; 0000-0002-2897-5892</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646560/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646560/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33178832$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Pizzimenti, Stefania</contributor><contributor>Stefania Pizzimenti</contributor><creatorcontrib>He, Mao-Lin</creatorcontrib><creatorcontrib>Gu, Yong-Yao</creatorcontrib><creatorcontrib>Huang, Zhi-Guang</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Cheng, Ji-Wen</creatorcontrib><creatorcontrib>Li, Sheng-Hua</creatorcontrib><creatorcontrib>Sun, Yu</creatorcontrib><creatorcontrib>Yan, Hai-Biao</creatorcontrib><title>Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.</description><subject>Adenosine triphosphatase</subject><subject>Archives &amp; records</subject><subject>Bone cancer</subject><subject>Bone Neoplasms - secondary</subject><subject>Cancer therapies</subject><subject>Carcinogenesis</subject><subject>Carcinogenesis - genetics</subject><subject>CDC2 Protein Kinase - metabolism</subject><subject>Chromosomes</subject><subject>Complications and side effects</subject><subject>Correlation analysis</subject><subject>Down-Regulation - genetics</subject><subject>Enrichment</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Ontology</subject><subject>Gene Regulatory Networks</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>mRNA</subject><subject>Network analysis</subject><subject>Ontology</subject><subject>p53 Protein</subject><subject>Pancreatic cancer</subject><subject>Patient outcomes</subject><subject>Phospholipid-translocating ATPase</subject><subject>Phospholipids</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - diagnosis</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Protein expression</subject><subject>Protein Interaction Maps - genetics</subject><subject>Proteins</subject><subject>Reproducibility of Results</subject><subject>Ribonucleic acid</subject><subject>Risk factors</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>ROC Curve</subject><subject>Signal transduction</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Target acquisition</subject><subject>Transfection</subject><subject>Tumorigenesis</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkUuP0zAUhS0EYkZldqxRJDZIEMaOH7E3SKUMD2l4CHVvuc5161FiFzth4N_jqKUDrPDG1vV3z30chB4T_JIQzi8b3OBLgWnLKLuHzhtKWC0II_dPb0rP0EXON7gcSQRW4iE6o5S0UtLmHI1v4m1IsJ16M_oYquiqwX_9tKwbzKurH_sEOc9xE7rqtY993Hpr-uoj2J0JPg-VD9WXFPNoRqhWJlhI1XoaYvJbCJB9PmTGACVnNIUrsUfogTN9hovjvUDrt1fr1fv6-vO7D6vldW2ZUmMNkjoKbcfxBmNrpeObFneWCemEwi1wIawwnROC8JYJ7JTqsDEKE2YMa-gCvTrI7qfNAJ2FMCbT633yg0k_dTRe__0T_E5v43fdCiZ42eoCPTsKpPhtgjzqwWcLfW8CxCnrphTFZY1krvX0H_QmTimU6QrFJWu5auQdtTU9aB9cLHXtLKqXQrWYSCVJoV4cKFsWmxO4U8sE69l2Pduuj7YX_MmfY57g3yYX4PkB2PnQmVv_n3JQGHDmjiaUMyroLxxAvaY</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>He, Mao-Lin</creator><creator>Gu, Yong-Yao</creator><creator>Huang, Zhi-Guang</creator><creator>Chen, Gang</creator><creator>Cheng, Ji-Wen</creator><creator>Li, Sheng-Hua</creator><creator>Sun, Yu</creator><creator>Yan, Hai-Biao</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>John Wiley &amp; 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Gu, Yong-Yao ; Huang, Zhi-Guang ; Chen, Gang ; Cheng, Ji-Wen ; Li, Sheng-Hua ; Sun, Yu ; Yan, Hai-Biao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-e83f3e7d50b00cc8f5b70dc468f6907e566c6adf66157460f99d0aa9014aa423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenosine triphosphatase</topic><topic>Archives &amp; records</topic><topic>Bone cancer</topic><topic>Bone Neoplasms - secondary</topic><topic>Cancer therapies</topic><topic>Carcinogenesis</topic><topic>Carcinogenesis - genetics</topic><topic>CDC2 Protein Kinase - metabolism</topic><topic>Chromosomes</topic><topic>Complications and side effects</topic><topic>Correlation analysis</topic><topic>Down-Regulation - genetics</topic><topic>Enrichment</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Ontology</topic><topic>Gene Regulatory Networks</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kaplan-Meier Estimate</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>mRNA</topic><topic>Network analysis</topic><topic>Ontology</topic><topic>p53 Protein</topic><topic>Pancreatic cancer</topic><topic>Patient outcomes</topic><topic>Phospholipid-translocating ATPase</topic><topic>Phospholipids</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - diagnosis</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Protein expression</topic><topic>Protein Interaction Maps - genetics</topic><topic>Proteins</topic><topic>Reproducibility of Results</topic><topic>Ribonucleic acid</topic><topic>Risk factors</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>ROC Curve</topic><topic>Signal transduction</topic><topic>Statistical analysis</topic><topic>Statistical methods</topic><topic>Target acquisition</topic><topic>Transfection</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Mao-Lin</creatorcontrib><creatorcontrib>Gu, Yong-Yao</creatorcontrib><creatorcontrib>Huang, Zhi-Guang</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Cheng, Ji-Wen</creatorcontrib><creatorcontrib>Li, Sheng-Hua</creatorcontrib><creatorcontrib>Sun, Yu</creatorcontrib><creatorcontrib>Yan, Hai-Biao</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health &amp; 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The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>33178832</pmid><doi>10.1155/2020/6037434</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-0709-8509</orcidid><orcidid>https://orcid.org/0000-0002-2897-5892</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adenosine triphosphatase
Archives & records
Bone cancer
Bone Neoplasms - secondary
Cancer therapies
Carcinogenesis
Carcinogenesis - genetics
CDC2 Protein Kinase - metabolism
Chromosomes
Complications and side effects
Correlation analysis
Down-Regulation - genetics
Enrichment
Gene expression
Gene Expression Regulation, Neoplastic
Gene Ontology
Gene Regulatory Networks
Genes
Genetic aspects
Genomes
Health aspects
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Metastases
Metastasis
MicroRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
miRNA
mRNA
Network analysis
Ontology
p53 Protein
Pancreatic cancer
Patient outcomes
Phospholipid-translocating ATPase
Phospholipids
Prognosis
Prostate cancer
Prostatic Neoplasms - diagnosis
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Protein expression
Protein Interaction Maps - genetics
Proteins
Reproducibility of Results
Ribonucleic acid
Risk factors
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
ROC Curve
Signal transduction
Statistical analysis
Statistical methods
Target acquisition
Transfection
Tumorigenesis
title Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis
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