Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis
Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal can...
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Veröffentlicht in: | Journal of cellular physiology 2019-11, Vol.234 (11), p.20816-20828 |
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creator | Tang, Dongxin Yang, Zhu Long, Fengxi Luo, Li Yang, Bing Zhu, Ruyi Sang, Xianan Cao, Gang Wang, Kuilong |
description | Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR‐20b‐5p is negatively correlated with that of metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR‐20b‐5p, and Oct4. We proceeded to show that both si‐MALAT1 and miR‐20b‐5p‐mimic attenuated microsphere formation and self‐renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex‐determining region Y‐box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT‐116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si‐MALAT1 or miR‐20b‐5p‐mimic suppressed the tumorigenicity of HCT‐116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance‐related factor Oct4 by miR‐20b‐5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.
We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated. |
doi_str_mv | 10.1002/jcp.28687 |
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We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.28687</identifier><identifier>PMID: 31012108</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adenocarcinoma ; Cancer ; cancer stem cells ; Cell self-renewal ; Chemotherapy ; Colorectal cancer ; Colorectal carcinoma ; Glucose metabolism ; Glucose transporter ; Hexokinase ; Kinases ; L-Lactate dehydrogenase ; Lactate dehydrogenase ; Lactic acid ; Lung cancer ; Lungs ; MALAT1 ; Metastases ; Metastasis ; miRNA ; miR‐20b‐5p/Oct4 axis ; Notch1 protein ; Oct-4 protein ; Pyruvate kinase ; Pyruvic acid ; Stem cell transplantation ; Stem cells ; stemness ; Transcription ; Tumorigenicity ; Tumors ; Xenografts ; Xenotransplantation</subject><ispartof>Journal of cellular physiology, 2019-11, Vol.234 (11), p.20816-20828</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3537-72b736f3e0f55f5e70ac69dc4f535bb8da9f3e48492d8d63110fbab14483bb853</citedby><cites>FETCH-LOGICAL-c3537-72b736f3e0f55f5e70ac69dc4f535bb8da9f3e48492d8d63110fbab14483bb853</cites><orcidid>0000-0002-7776-7387</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.28687$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.28687$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31012108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Dongxin</creatorcontrib><creatorcontrib>Yang, Zhu</creatorcontrib><creatorcontrib>Long, Fengxi</creatorcontrib><creatorcontrib>Luo, Li</creatorcontrib><creatorcontrib>Yang, Bing</creatorcontrib><creatorcontrib>Zhu, Ruyi</creatorcontrib><creatorcontrib>Sang, Xianan</creatorcontrib><creatorcontrib>Cao, Gang</creatorcontrib><creatorcontrib>Wang, Kuilong</creatorcontrib><title>Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR‐20b‐5p is negatively correlated with that of metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR‐20b‐5p, and Oct4. We proceeded to show that both si‐MALAT1 and miR‐20b‐5p‐mimic attenuated microsphere formation and self‐renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex‐determining region Y‐box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT‐116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si‐MALAT1 or miR‐20b‐5p‐mimic suppressed the tumorigenicity of HCT‐116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance‐related factor Oct4 by miR‐20b‐5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.
We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.</description><subject>Adenocarcinoma</subject><subject>Cancer</subject><subject>cancer stem cells</subject><subject>Cell self-renewal</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Glucose metabolism</subject><subject>Glucose transporter</subject><subject>Hexokinase</subject><subject>Kinases</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Lung cancer</subject><subject>Lungs</subject><subject>MALAT1</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>miRNA</subject><subject>miR‐20b‐5p/Oct4 axis</subject><subject>Notch1 protein</subject><subject>Oct-4 protein</subject><subject>Pyruvate kinase</subject><subject>Pyruvic acid</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>stemness</subject><subject>Transcription</subject><subject>Tumorigenicity</subject><subject>Tumors</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kU9P2zAchi3EREu3w74AssRlHNL6b_4cqwoYU6ETYufIcRxwl8TBTjR647TzPuM-Cb-2jMMkLral9_Gjn_0i9JmSKSWEzda6m7I0TpMDNKYkSyIRS3aIxpDRKJOCjtBxCGtCSJZxfoRGnBLKKEnH6PfStfe4da12pYXT7c0cX8-X8zuKG1Na1ZuAQ28arE1d_33-U9ufBnfedcb3FjLb4oehUS3Wrnbe6F7VWKtWG7-7EXCxwd7cD7Xqt_rG3oKEkQJW2c1WuhdYPdnwEX2oVB3Mp9d9gn5cnN8tvkbL1eXVYr6MNJc8iRJWJDyuuCGVlJU0CVE6zkotKsllUaSlyiAUqchYmZYxp5RUhSqoECmHWPIJ-rL3whMeBxP6vLFhO6hqjRtCzhjlVHImEkBP_0PXbvAtTAcUqGOayBSosz2lvQvBmyrvvG2U3-SU5Ntycign35UD7MmrcSjgc9_If20AMNsDv2xtNu-b8m-L73vlCzZZmqk</recordid><startdate>201911</startdate><enddate>201911</enddate><creator>Tang, Dongxin</creator><creator>Yang, Zhu</creator><creator>Long, Fengxi</creator><creator>Luo, Li</creator><creator>Yang, Bing</creator><creator>Zhu, Ruyi</creator><creator>Sang, Xianan</creator><creator>Cao, Gang</creator><creator>Wang, Kuilong</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7776-7387</orcidid></search><sort><creationdate>201911</creationdate><title>Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis</title><author>Tang, Dongxin ; Yang, Zhu ; Long, Fengxi ; Luo, Li ; Yang, Bing ; Zhu, Ruyi ; Sang, Xianan ; Cao, Gang ; Wang, Kuilong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3537-72b736f3e0f55f5e70ac69dc4f535bb8da9f3e48492d8d63110fbab14483bb853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adenocarcinoma</topic><topic>Cancer</topic><topic>cancer stem cells</topic><topic>Cell self-renewal</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Glucose metabolism</topic><topic>Glucose transporter</topic><topic>Hexokinase</topic><topic>Kinases</topic><topic>L-Lactate dehydrogenase</topic><topic>Lactate dehydrogenase</topic><topic>Lactic acid</topic><topic>Lung cancer</topic><topic>Lungs</topic><topic>MALAT1</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>miRNA</topic><topic>miR‐20b‐5p/Oct4 axis</topic><topic>Notch1 protein</topic><topic>Oct-4 protein</topic><topic>Pyruvate kinase</topic><topic>Pyruvic acid</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>stemness</topic><topic>Transcription</topic><topic>Tumorigenicity</topic><topic>Tumors</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Dongxin</creatorcontrib><creatorcontrib>Yang, Zhu</creatorcontrib><creatorcontrib>Long, Fengxi</creatorcontrib><creatorcontrib>Luo, Li</creatorcontrib><creatorcontrib>Yang, Bing</creatorcontrib><creatorcontrib>Zhu, Ruyi</creatorcontrib><creatorcontrib>Sang, Xianan</creatorcontrib><creatorcontrib>Cao, Gang</creatorcontrib><creatorcontrib>Wang, Kuilong</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Dongxin</au><au>Yang, Zhu</au><au>Long, Fengxi</au><au>Luo, Li</au><au>Yang, Bing</au><au>Zhu, Ruyi</au><au>Sang, Xianan</au><au>Cao, Gang</au><au>Wang, Kuilong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2019-11</date><risdate>2019</risdate><volume>234</volume><issue>11</issue><spage>20816</spage><epage>20828</epage><pages>20816-20828</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR‐20b‐5p is negatively correlated with that of metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1, r = −0.928, p = 0.023) and Oct4 (r = −0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR‐20b‐5p, and Oct4. We proceeded to show that both si‐MALAT1 and miR‐20b‐5p‐mimic attenuated microsphere formation and self‐renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex‐determining region Y‐box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT‐116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si‐MALAT1 or miR‐20b‐5p‐mimic suppressed the tumorigenicity of HCT‐116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance‐related factor Oct4 by miR‐20b‐5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of CRC cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.
We present the possible underlying effects of MALAT1 in influencing the stem cell‐like properties of colorectal cancer cells. We propose that microRNAs and long noncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31012108</pmid><doi>10.1002/jcp.28687</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-7776-7387</orcidid></addata></record> |
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subjects | Adenocarcinoma Cancer cancer stem cells Cell self-renewal Chemotherapy Colorectal cancer Colorectal carcinoma Glucose metabolism Glucose transporter Hexokinase Kinases L-Lactate dehydrogenase Lactate dehydrogenase Lactic acid Lung cancer Lungs MALAT1 Metastases Metastasis miRNA miR‐20b‐5p/Oct4 axis Notch1 protein Oct-4 protein Pyruvate kinase Pyruvic acid Stem cell transplantation Stem cells stemness Transcription Tumorigenicity Tumors Xenografts Xenotransplantation |
title | Long noncoding RNA MALAT1 mediates stem cell‐like properties in human colorectal cancer cells by regulating miR‐20b‐5p/Oct4 axis |
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