Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway

Objective: To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. Methods: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set en...

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Veröffentlicht in:Cancer biology & therapy 2018-12, Vol.19 (12), p.1139-1152
Hauptverfasser: Chen, Fukun, Feng, Zhiping, Zhu, Jialun, Liu, Pengjie, Yang, Chuanzhou, Huang, Rongkai, Deng, Zhiyong
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container_end_page 1152
container_issue 12
container_start_page 1139
container_title Cancer biology & therapy
container_volume 19
creator Chen, Fukun
Feng, Zhiping
Zhu, Jialun
Liu, Pengjie
Yang, Chuanzhou
Huang, Rongkai
Deng, Zhiyong
description Objective: To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. Methods: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis. The mRNA and protein expressions in thyroid cancer tissues and cells were detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R digestion and nucleic acid electrophoresis. The target relationships were verified by the dual luciferase reporter assay. Cell viability, invasion and apoptosis were determined by MTT assay, Transwell assay and flow cytometry, respectively. Results: CircNEK6 and FZD8 were significantly up-regulated in thyroid cancer, with strong correlations. The Wnt signaling pathway was activated in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8, and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8 could promote the growth and invasion of thyroid cancer cells, while up-regulation of miR-370-3p could suppress thyroid cancer progression and inhibit the Wnt signaling pathway. MiR-370-3p's effect on thyroid cancer cells could be rescued by circNEK6 or FZD8. Conclusion: CircNEK6 promoted the progression of thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by targeting miR-370-3p.
doi_str_mv 10.1080/15384047.2018.1480888
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Methods: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis. The mRNA and protein expressions in thyroid cancer tissues and cells were detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R digestion and nucleic acid electrophoresis. The target relationships were verified by the dual luciferase reporter assay. Cell viability, invasion and apoptosis were determined by MTT assay, Transwell assay and flow cytometry, respectively. Results: CircNEK6 and FZD8 were significantly up-regulated in thyroid cancer, with strong correlations. The Wnt signaling pathway was activated in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8, and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8 could promote the growth and invasion of thyroid cancer cells, while up-regulation of miR-370-3p could suppress thyroid cancer progression and inhibit the Wnt signaling pathway. MiR-370-3p's effect on thyroid cancer cells could be rescued by circNEK6 or FZD8. Conclusion: CircNEK6 promoted the progression of thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by targeting miR-370-3p.</description><identifier>ISSN: 1538-4047</identifier><identifier>EISSN: 1555-8576</identifier><identifier>DOI: 10.1080/15384047.2018.1480888</identifier><identifier>PMID: 30207869</identifier><language>eng</language><publisher>United States: Taylor &amp; Francis</publisher><subject>Binding Sites ; Cell Line, Tumor ; Cell Movement - genetics ; Cell Proliferation - genetics ; Cell Survival - genetics ; circRNA ; FZD8 ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; GSEA ; Humans ; KEGG ; MicroRNAs - genetics ; miR-370-3p ; Models, Biological ; NIMA-Related Kinases - genetics ; Research Paper ; RNA - genetics ; RNA Interference ; RNA, Circular ; thyroid cancer ; Thyroid Neoplasms - genetics ; Thyroid Neoplasms - metabolism ; Thyroid Neoplasms - pathology ; Wnt Signaling Pathway</subject><ispartof>Cancer biology &amp; therapy, 2018-12, Vol.19 (12), p.1139-1152</ispartof><rights>2018 Taylor &amp; Francis Group, LLC 2018</rights><rights>2018 Taylor &amp; Francis Group, LLC 2018 Taylor &amp; Francis</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-e0b3223fe970afc4d26d047734c776e019420e434e628e113ae17ec5206d34473</citedby><cites>FETCH-LOGICAL-c534t-e0b3223fe970afc4d26d047734c776e019420e434e628e113ae17ec5206d34473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301817/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301817/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30207869$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Fukun</creatorcontrib><creatorcontrib>Feng, Zhiping</creatorcontrib><creatorcontrib>Zhu, Jialun</creatorcontrib><creatorcontrib>Liu, Pengjie</creatorcontrib><creatorcontrib>Yang, Chuanzhou</creatorcontrib><creatorcontrib>Huang, Rongkai</creatorcontrib><creatorcontrib>Deng, Zhiyong</creatorcontrib><title>Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway</title><title>Cancer biology &amp; therapy</title><addtitle>Cancer Biol Ther</addtitle><description>Objective: To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. Methods: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis. The mRNA and protein expressions in thyroid cancer tissues and cells were detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R digestion and nucleic acid electrophoresis. The target relationships were verified by the dual luciferase reporter assay. Cell viability, invasion and apoptosis were determined by MTT assay, Transwell assay and flow cytometry, respectively. Results: CircNEK6 and FZD8 were significantly up-regulated in thyroid cancer, with strong correlations. The Wnt signaling pathway was activated in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8, and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8 could promote the growth and invasion of thyroid cancer cells, while up-regulation of miR-370-3p could suppress thyroid cancer progression and inhibit the Wnt signaling pathway. MiR-370-3p's effect on thyroid cancer cells could be rescued by circNEK6 or FZD8. Conclusion: CircNEK6 promoted the progression of thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by targeting miR-370-3p.</description><subject>Binding Sites</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - genetics</subject><subject>Cell Proliferation - genetics</subject><subject>Cell Survival - genetics</subject><subject>circRNA</subject><subject>FZD8</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Regulatory Networks</subject><subject>GSEA</subject><subject>Humans</subject><subject>KEGG</subject><subject>MicroRNAs - genetics</subject><subject>miR-370-3p</subject><subject>Models, Biological</subject><subject>NIMA-Related Kinases - genetics</subject><subject>Research Paper</subject><subject>RNA - genetics</subject><subject>RNA Interference</subject><subject>RNA, Circular</subject><subject>thyroid cancer</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - metabolism</subject><subject>Thyroid Neoplasms - pathology</subject><subject>Wnt Signaling Pathway</subject><issn>1538-4047</issn><issn>1555-8576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UUtv1DAQjhCIlsJPAPnIJVu_YjsXRFVtoaIqUgXiaLnOJGuU2MH2brVH_jmOdlvBhdN49D1mPF9VvSV4RbDC56RhimMuVxQTtSJcYaXUs-qUNE1Tq0aK58ubqXohnVSvUvqJMZVUtC-rE4Yplkq0p9Xv9QRxcH5AMYyQUOiRddHe3V7o2_UXgbKJA-QFn9xdzSSu2YycR3kDaC4S10M02QWPjO8KsDNpaYpN3uxjcB2yxluIaOcM-uEzSm7wZlwMZ5M3D2b_unrRmzHBm2M9q75frb9dfq5vvn66vry4qW3DeK4B3zNKWQ-txKa3vKOiKz-TjFspBWDScoqBMw6CKiCEGSASbEOx6Bjnkp1VHw6-8_Z-gs6Cz9GMeo5uMnGvg3H6X8S7jR7CTgtWLkwWg_dHgxh-bSFlPblkYRyNh7BNmhLMhGilooXaHKg2hpQi9E9jCNZLfPoxPr3Ep4_xFd27v3d8Uj3mVQgfDwTn-xAn8xDi2Ols9mOIfSyXdkmz_8_4A-AVqnc</recordid><startdate>20181202</startdate><enddate>20181202</enddate><creator>Chen, Fukun</creator><creator>Feng, Zhiping</creator><creator>Zhu, Jialun</creator><creator>Liu, Pengjie</creator><creator>Yang, Chuanzhou</creator><creator>Huang, Rongkai</creator><creator>Deng, Zhiyong</creator><general>Taylor &amp; Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20181202</creationdate><title>Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway</title><author>Chen, Fukun ; Feng, Zhiping ; Zhu, Jialun ; Liu, Pengjie ; Yang, Chuanzhou ; Huang, Rongkai ; Deng, Zhiyong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-e0b3223fe970afc4d26d047734c776e019420e434e628e113ae17ec5206d34473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Binding Sites</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - genetics</topic><topic>Cell Proliferation - genetics</topic><topic>Cell Survival - genetics</topic><topic>circRNA</topic><topic>FZD8</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene Regulatory Networks</topic><topic>GSEA</topic><topic>Humans</topic><topic>KEGG</topic><topic>MicroRNAs - genetics</topic><topic>miR-370-3p</topic><topic>Models, Biological</topic><topic>NIMA-Related Kinases - genetics</topic><topic>Research Paper</topic><topic>RNA - genetics</topic><topic>RNA Interference</topic><topic>RNA, Circular</topic><topic>thyroid cancer</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - metabolism</topic><topic>Thyroid Neoplasms - pathology</topic><topic>Wnt Signaling Pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Fukun</creatorcontrib><creatorcontrib>Feng, Zhiping</creatorcontrib><creatorcontrib>Zhu, Jialun</creatorcontrib><creatorcontrib>Liu, Pengjie</creatorcontrib><creatorcontrib>Yang, Chuanzhou</creatorcontrib><creatorcontrib>Huang, Rongkai</creatorcontrib><creatorcontrib>Deng, Zhiyong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer biology &amp; therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Fukun</au><au>Feng, Zhiping</au><au>Zhu, Jialun</au><au>Liu, Pengjie</au><au>Yang, Chuanzhou</au><au>Huang, Rongkai</au><au>Deng, Zhiyong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway</atitle><jtitle>Cancer biology &amp; therapy</jtitle><addtitle>Cancer Biol Ther</addtitle><date>2018-12-02</date><risdate>2018</risdate><volume>19</volume><issue>12</issue><spage>1139</spage><epage>1152</epage><pages>1139-1152</pages><issn>1538-4047</issn><eissn>1555-8576</eissn><abstract>Objective: To identify the significantly altered circRNAs and mRNAs in thyroid cancer, investigate their target miRNAs and determine their biological functions. Methods: The differentially expressed circRNAs, mRNAs and pathways in thyroid cancer were identified by microarray analysis and gene set enrichment analysis (GSEA). The correlative circRNAs and mRNAs were found out through Pearson correlative analysis. The common target miRNAs of circNEK6 and FZD8 related to thyroid cancer was screened out through Targetscan, miRanda and HMDD analysis. The mRNA and protein expressions in thyroid cancer tissues and cells were detected by qRT-PCR and western blot. CircRNA was confirmed by the RNase R digestion and nucleic acid electrophoresis. The target relationships were verified by the dual luciferase reporter assay. Cell viability, invasion and apoptosis were determined by MTT assay, Transwell assay and flow cytometry, respectively. Results: CircNEK6 and FZD8 were significantly up-regulated in thyroid cancer, with strong correlations. The Wnt signaling pathway was activated in thyroid cancer. MiR-370-3p was the common target miRNA of circNEK6 and FZD8, and it was down-regulated in thyroid cancer. Overexpression of circNEK6 and FZD8 could promote the growth and invasion of thyroid cancer cells, while up-regulation of miR-370-3p could suppress thyroid cancer progression and inhibit the Wnt signaling pathway. MiR-370-3p's effect on thyroid cancer cells could be rescued by circNEK6 or FZD8. Conclusion: CircNEK6 promoted the progression of thyroid cancer through up-regulating FZD8 and activating Wnt signaling pathway by targeting miR-370-3p.</abstract><cop>United States</cop><pub>Taylor &amp; Francis</pub><pmid>30207869</pmid><doi>10.1080/15384047.2018.1480888</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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subjects Binding Sites
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
Cell Survival - genetics
circRNA
FZD8
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
GSEA
Humans
KEGG
MicroRNAs - genetics
miR-370-3p
Models, Biological
NIMA-Related Kinases - genetics
Research Paper
RNA - genetics
RNA Interference
RNA, Circular
thyroid cancer
Thyroid Neoplasms - genetics
Thyroid Neoplasms - metabolism
Thyroid Neoplasms - pathology
Wnt Signaling Pathway
title Emerging roles of circRNA_NEK6 targeting miR-370-3p in the proliferation and invasion of thyroid cancer via Wnt signaling pathway
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