Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A
Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains...
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| Veröffentlicht in: | Life sciences (1973) 2021-07, Vol.277, p.119398-119398, Article 119398 |
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| creator | Wang, Di Feng, Meina Ma, Xianxiong Tao, Kaixiong Wang, Guobin |
| description | Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains unexplored. Many studies have suggested a close correlation between the transcription factor (TF)-miRNA signal and cancer. The present study explored the effects of TF-miR-146b-3p axis on CRC and elucidated its downstream regulatory molecule.
The expression levels of miR-146b-3p in CRC tissues and cell lines were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). The impact of miR-146b-3p on CRC cell proliferation, migration, and invasion were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay and transwell migration and invasion assay. Additionally, the impact of miR-146b-3p on CRC cell cycle and apoptosis was investigated using flow cytometry. The targets of miR-146b-3p, predicted by miRWalk database, were verified using a dual-luciferase reporter system. The expression levels of TFs were detected using qRT-PCR. The effects of miR-146b-3p and SP1 on FAM107A expression were assessed by performing qRT-PCR and western blotting. Chromatin Immunoprecipitation (ChIP) Assay was performed and JASPAR database was utilized to explore the regulatory relationship between the SP1 and miR-146b-3p.
Increased expression of miR-146b-3p in CRC tissues and cell lines correlated with poor overall survival (OS). Upregulation of miR-146b-3p expression remarkably promoted the proliferation, migration, and invasion of CRC cells and suppressed their apoptosis. Furthermore, SP1 overexpression significantly elevated the miR-146b-3p expression, decreased the FAM107A expression, and promoted the G1/S transition. The miR-146b-3p overexpression also enhanced the effects of SP1 overexpression on CRC cell proliferation, migration, and invasion, whereas miR-146b-3p knockdown led to the opposite results.
Mechanistically, miR-146b-3p functions as an oncogene by directly targeting FAM107A. Our results highlight the critical regulatory role played by SP1-induced miR-146b-3p expression in CRC development. Our results suggest that SP1/miR-146b-3p/FAM107A axis may be a potential therapeutic target for CRC. |
| doi_str_mv | 10.1016/j.lfs.2021.119398 |
| format | Article |
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The expression levels of miR-146b-3p in CRC tissues and cell lines were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). The impact of miR-146b-3p on CRC cell proliferation, migration, and invasion were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay and transwell migration and invasion assay. Additionally, the impact of miR-146b-3p on CRC cell cycle and apoptosis was investigated using flow cytometry. The targets of miR-146b-3p, predicted by miRWalk database, were verified using a dual-luciferase reporter system. The expression levels of TFs were detected using qRT-PCR. The effects of miR-146b-3p and SP1 on FAM107A expression were assessed by performing qRT-PCR and western blotting. Chromatin Immunoprecipitation (ChIP) Assay was performed and JASPAR database was utilized to explore the regulatory relationship between the SP1 and miR-146b-3p.
Increased expression of miR-146b-3p in CRC tissues and cell lines correlated with poor overall survival (OS). Upregulation of miR-146b-3p expression remarkably promoted the proliferation, migration, and invasion of CRC cells and suppressed their apoptosis. Furthermore, SP1 overexpression significantly elevated the miR-146b-3p expression, decreased the FAM107A expression, and promoted the G1/S transition. The miR-146b-3p overexpression also enhanced the effects of SP1 overexpression on CRC cell proliferation, migration, and invasion, whereas miR-146b-3p knockdown led to the opposite results.
Mechanistically, miR-146b-3p functions as an oncogene by directly targeting FAM107A. Our results highlight the critical regulatory role played by SP1-induced miR-146b-3p expression in CRC development. Our results suggest that SP1/miR-146b-3p/FAM107A axis may be a potential therapeutic target for CRC.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/j.lfs.2021.119398</identifier><identifier>PMID: 33831429</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Adult ; Aged ; Animals ; Apoptosis ; Apoptosis - genetics ; ArrayExpress ; Assaying ; Cancer ; Cell cycle ; Cell Cycle - genetics ; Cell growth ; Cell Line, Tumor ; Cell migration ; Cell Movement - genetics ; Cell proliferation ; Cell Proliferation - drug effects ; Chromatin ; Colorectal Cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - metabolism ; Downstream effects ; FAM107A ; Female ; Flow cytometry ; Gene Expression Regulation, Neoplastic - genetics ; Genes, Tumor Suppressor - physiology ; GEO ; Humans ; Immunoprecipitation ; Male ; Metastases ; Mice ; Mice, Inbred BALB C ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; MiR-146b-3p ; miRNA ; Neoplasm Metastasis - genetics ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Polymerase chain reaction ; Ribonucleic acid ; RNA ; SP1 ; Sp1 Transcription Factor - genetics ; Sp1 Transcription Factor - metabolism ; Transcription factors ; Tumors ; Western blotting ; Xenograft Model Antitumor Assays</subject><ispartof>Life sciences (1973), 2021-07, Vol.277, p.119398-119398, Article 119398</ispartof><rights>2021</rights><rights>Copyright © 2021. Published by Elsevier Inc.</rights><rights>Copyright Elsevier BV Jul 15, 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-9bec298f31a399a39013bae4c8f9ee5c4bfad3afb049af35c2a4327d0509ac6d3</citedby><cites>FETCH-LOGICAL-c381t-9bec298f31a399a39013bae4c8f9ee5c4bfad3afb049af35c2a4327d0509ac6d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lfs.2021.119398$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33831429$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Di</creatorcontrib><creatorcontrib>Feng, Meina</creatorcontrib><creatorcontrib>Ma, Xianxiong</creatorcontrib><creatorcontrib>Tao, Kaixiong</creatorcontrib><creatorcontrib>Wang, Guobin</creatorcontrib><title>Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains unexplored. Many studies have suggested a close correlation between the transcription factor (TF)-miRNA signal and cancer. The present study explored the effects of TF-miR-146b-3p axis on CRC and elucidated its downstream regulatory molecule.
The expression levels of miR-146b-3p in CRC tissues and cell lines were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). The impact of miR-146b-3p on CRC cell proliferation, migration, and invasion were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay and transwell migration and invasion assay. Additionally, the impact of miR-146b-3p on CRC cell cycle and apoptosis was investigated using flow cytometry. The targets of miR-146b-3p, predicted by miRWalk database, were verified using a dual-luciferase reporter system. The expression levels of TFs were detected using qRT-PCR. The effects of miR-146b-3p and SP1 on FAM107A expression were assessed by performing qRT-PCR and western blotting. Chromatin Immunoprecipitation (ChIP) Assay was performed and JASPAR database was utilized to explore the regulatory relationship between the SP1 and miR-146b-3p.
Increased expression of miR-146b-3p in CRC tissues and cell lines correlated with poor overall survival (OS). Upregulation of miR-146b-3p expression remarkably promoted the proliferation, migration, and invasion of CRC cells and suppressed their apoptosis. Furthermore, SP1 overexpression significantly elevated the miR-146b-3p expression, decreased the FAM107A expression, and promoted the G1/S transition. The miR-146b-3p overexpression also enhanced the effects of SP1 overexpression on CRC cell proliferation, migration, and invasion, whereas miR-146b-3p knockdown led to the opposite results.
Mechanistically, miR-146b-3p functions as an oncogene by directly targeting FAM107A. Our results highlight the critical regulatory role played by SP1-induced miR-146b-3p expression in CRC development. Our results suggest that SP1/miR-146b-3p/FAM107A axis may be a potential therapeutic target for CRC.</description><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>ArrayExpress</subject><subject>Assaying</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell Cycle - genetics</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Chromatin</subject><subject>Colorectal Cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - metabolism</subject><subject>Downstream effects</subject><subject>FAM107A</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>GEO</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Male</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>MiR-146b-3p</subject><subject>miRNA</subject><subject>Neoplasm Metastasis - genetics</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Polymerase chain reaction</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>SP1</subject><subject>Sp1 Transcription Factor - genetics</subject><subject>Sp1 Transcription Factor - metabolism</subject><subject>Transcription factors</subject><subject>Tumors</subject><subject>Western blotting</subject><subject>Xenograft Model Antitumor Assays</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS0EotvCB-CCLHHhksVjJ5tYnFZVS5HKH0E5WxNnvHiVjRfbqcQ34GPjaAsHDkgzmsvvPY3eY-wFiDUI2LzZr0eX1lJIWANopbtHbAVdqyuxUfCYrYSQdaWkaM7YeUp7IUTTtOopO1OqU1BLvWK_7iJOyUZ_zD5M3KHNIfKvn6Hy0zBbGvjB2xi-fNxWUG_6Sh0Xxo8-Y6bE83fixxh2kVJa9DgVAWVMZXziwXEbxhDJZhy5xclS5PceeaTdPGL2045fbz-AaLfP2BOHY6LnD_eCfbu-uru8qW4_vXt_ub2trOogV7onK3XnFKDSuqwA1SPVtnOaqLF173BQ6HpRa3SqsRJrJdtBNEKj3Qzqgr0--Za3f8yUsjn4ZGkccaIwJyMbAKla0JuCvvoH3Yc5TuW7QtW6WLZCFwpOVIkppUjOHKM_YPxpQJilJrM3pSaz1GRONRXNywfnuT_Q8Ffxp5cCvD0BVKK49xRNsp5KfINfwjRD8P-x_w25CKMV</recordid><startdate>20210715</startdate><enddate>20210715</enddate><creator>Wang, Di</creator><creator>Feng, Meina</creator><creator>Ma, Xianxiong</creator><creator>Tao, Kaixiong</creator><creator>Wang, Guobin</creator><general>Elsevier Inc</general><general>Elsevier BV</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20210715</creationdate><title>Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A</title><author>Wang, Di ; Feng, Meina ; Ma, Xianxiong ; Tao, Kaixiong ; Wang, Guobin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-9bec298f31a399a39013bae4c8f9ee5c4bfad3afb049af35c2a4327d0509ac6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>ArrayExpress</topic><topic>Assaying</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell Cycle - genetics</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement - genetics</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Chromatin</topic><topic>Colorectal Cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Downstream effects</topic><topic>FAM107A</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>GEO</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Male</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>MiR-146b-3p</topic><topic>miRNA</topic><topic>Neoplasm Metastasis - genetics</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Polymerase chain reaction</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>SP1</topic><topic>Sp1 Transcription Factor - genetics</topic><topic>Sp1 Transcription Factor - metabolism</topic><topic>Transcription factors</topic><topic>Tumors</topic><topic>Western blotting</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Di</creatorcontrib><creatorcontrib>Feng, Meina</creatorcontrib><creatorcontrib>Ma, Xianxiong</creatorcontrib><creatorcontrib>Tao, Kaixiong</creatorcontrib><creatorcontrib>Wang, Guobin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Di</au><au>Feng, Meina</au><au>Ma, Xianxiong</au><au>Tao, Kaixiong</au><au>Wang, Guobin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>2021-07-15</date><risdate>2021</risdate><volume>277</volume><spage>119398</spage><epage>119398</epage><pages>119398-119398</pages><artnum>119398</artnum><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>Recent studies have provided compelling evidence regarding the association of microRNAs (miRNAs) with the progression and development of tumors. Among the miRNAs, the dysregulation of miR-146b-3p expression has been reported in several cancers, however, its effect on colorectal cancer (CRC) remains unexplored. Many studies have suggested a close correlation between the transcription factor (TF)-miRNA signal and cancer. The present study explored the effects of TF-miR-146b-3p axis on CRC and elucidated its downstream regulatory molecule.
The expression levels of miR-146b-3p in CRC tissues and cell lines were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). The impact of miR-146b-3p on CRC cell proliferation, migration, and invasion were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell proliferation assay and transwell migration and invasion assay. Additionally, the impact of miR-146b-3p on CRC cell cycle and apoptosis was investigated using flow cytometry. The targets of miR-146b-3p, predicted by miRWalk database, were verified using a dual-luciferase reporter system. The expression levels of TFs were detected using qRT-PCR. The effects of miR-146b-3p and SP1 on FAM107A expression were assessed by performing qRT-PCR and western blotting. Chromatin Immunoprecipitation (ChIP) Assay was performed and JASPAR database was utilized to explore the regulatory relationship between the SP1 and miR-146b-3p.
Increased expression of miR-146b-3p in CRC tissues and cell lines correlated with poor overall survival (OS). Upregulation of miR-146b-3p expression remarkably promoted the proliferation, migration, and invasion of CRC cells and suppressed their apoptosis. Furthermore, SP1 overexpression significantly elevated the miR-146b-3p expression, decreased the FAM107A expression, and promoted the G1/S transition. The miR-146b-3p overexpression also enhanced the effects of SP1 overexpression on CRC cell proliferation, migration, and invasion, whereas miR-146b-3p knockdown led to the opposite results.
Mechanistically, miR-146b-3p functions as an oncogene by directly targeting FAM107A. Our results highlight the critical regulatory role played by SP1-induced miR-146b-3p expression in CRC development. Our results suggest that SP1/miR-146b-3p/FAM107A axis may be a potential therapeutic target for CRC.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>33831429</pmid><doi>10.1016/j.lfs.2021.119398</doi><tpages>1</tpages></addata></record> |
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| subjects | Adult Aged Animals Apoptosis Apoptosis - genetics ArrayExpress Assaying Cancer Cell cycle Cell Cycle - genetics Cell growth Cell Line, Tumor Cell migration Cell Movement - genetics Cell proliferation Cell Proliferation - drug effects Chromatin Colorectal Cancer Colorectal carcinoma Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Downstream effects FAM107A Female Flow cytometry Gene Expression Regulation, Neoplastic - genetics Genes, Tumor Suppressor - physiology GEO Humans Immunoprecipitation Male Metastases Mice Mice, Inbred BALB C MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Middle Aged MiR-146b-3p miRNA Neoplasm Metastasis - genetics Nuclear Proteins - genetics Nuclear Proteins - metabolism Polymerase chain reaction Ribonucleic acid RNA SP1 Sp1 Transcription Factor - genetics Sp1 Transcription Factor - metabolism Transcription factors Tumors Western blotting Xenograft Model Antitumor Assays |
| title | Transcription factor SP1-induced microRNA-146b-3p facilitates the progression and metastasis of colorectal cancer via regulating FAM107A |
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