Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines
The aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric canc...
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| Veröffentlicht in: | Cell death and differentiation 2021-09, Vol.28 (9), p.2708-2727 |
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| creator | Yang, Liping Hou, Yixuan Du, Yan-e Li, Qiao Zhou, Fanlin Li, Yu Zeng, Huan Jin, Ting Wan, Xueying Guan, Shengdong Wang, Rui Liu, Manran |
| description | The aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric cancer (GC) metastasis. MiR-4646-5p, one of Drosha-independent mirtronic miRNA, is aberrant up-regulated in Drosha-low expressed GC and Drosha-knockdown gastric cancer cells. Mirtronic miR-4646-5p is a specific transcription splicing product of intron 3 of the host gene
Abhd16a
with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate
Abhd16a
and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene
Abhd16a
mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer. |
| doi_str_mv | 10.1038/s41418-021-00779-y |
| format | Article |
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Abhd16a
with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate
Abhd16a
and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene
Abhd16a
mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer.</description><identifier>ISSN: 1350-9047</identifier><identifier>EISSN: 1476-5403</identifier><identifier>DOI: 10.1038/s41418-021-00779-y</identifier><identifier>PMID: 33875796</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/105 ; 13/51 ; 13/89 ; 13/95 ; 14 ; 38 ; 38/61 ; 38/77 ; 42 ; 45 ; 45/15 ; 59 ; 631/45/320 ; 631/67/322 ; 64 ; 82 ; Animals ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; Cell Biology ; Cell Cycle Analysis ; Chromosome 5 ; Cofilin ; Gastric cancer ; Humans ; Life Sciences ; Lipid metabolism ; Lysophospholipids - metabolism ; Male ; Metabolism ; Metabolites ; Metabolomics - methods ; Metastases ; Metastasis ; Mice ; Mice, Nude ; miRNA ; Monoacylglycerol Lipases - metabolism ; Neoplasm Metastasis ; Phosphatidylserine ; RhoA protein ; Stem Cells ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Transcription ; Transfection</subject><ispartof>Cell death and differentiation, 2021-09, Vol.28 (9), p.2708-2727</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-15e508eceb4a70c6ac87dbef8bf13a66e1f435d2dcad0f4af2ba80b067ba7cf3</citedby><cites>FETCH-LOGICAL-c474t-15e508eceb4a70c6ac87dbef8bf13a66e1f435d2dcad0f4af2ba80b067ba7cf3</cites><orcidid>0000-0002-3898-6878</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/PMC8408170/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408170/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33875796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Liping</creatorcontrib><creatorcontrib>Hou, Yixuan</creatorcontrib><creatorcontrib>Du, Yan-e</creatorcontrib><creatorcontrib>Li, Qiao</creatorcontrib><creatorcontrib>Zhou, Fanlin</creatorcontrib><creatorcontrib>Li, Yu</creatorcontrib><creatorcontrib>Zeng, Huan</creatorcontrib><creatorcontrib>Jin, Ting</creatorcontrib><creatorcontrib>Wan, Xueying</creatorcontrib><creatorcontrib>Guan, Shengdong</creatorcontrib><creatorcontrib>Wang, Rui</creatorcontrib><creatorcontrib>Liu, Manran</creatorcontrib><title>Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines</title><title>Cell death and differentiation</title><addtitle>Cell Death Differ</addtitle><addtitle>Cell Death Differ</addtitle><description>The aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric cancer (GC) metastasis. MiR-4646-5p, one of Drosha-independent mirtronic miRNA, is aberrant up-regulated in Drosha-low expressed GC and Drosha-knockdown gastric cancer cells. Mirtronic miR-4646-5p is a specific transcription splicing product of intron 3 of the host gene
Abhd16a
with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate
Abhd16a
and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene
Abhd16a
mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer.</description><subject>13/1</subject><subject>13/105</subject><subject>13/51</subject><subject>13/89</subject><subject>13/95</subject><subject>14</subject><subject>38</subject><subject>38/61</subject><subject>38/77</subject><subject>42</subject><subject>45</subject><subject>45/15</subject><subject>59</subject><subject>631/45/320</subject><subject>631/67/322</subject><subject>64</subject><subject>82</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Cell Cycle Analysis</subject><subject>Chromosome 5</subject><subject>Cofilin</subject><subject>Gastric cancer</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Lipid metabolism</subject><subject>Lysophospholipids - metabolism</subject><subject>Male</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics - methods</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>miRNA</subject><subject>Monoacylglycerol Lipases - metabolism</subject><subject>Neoplasm Metastasis</subject><subject>Phosphatidylserine</subject><subject>RhoA protein</subject><subject>Stem Cells</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Transcription</subject><subject>Transfection</subject><issn>1350-9047</issn><issn>1476-5403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUtv1TAQhS0EoqXwB1igSGzYBMaxY_tukG7Lo0hFSKh7y3Ymua4SO9gJUv49preUx4KVx55vzvjoEPKcwmsKTL3JnHKqamhoDSDlrt4ekFPKpahbDuxhqVkL9Q64PCFPcr4BACF34jE5YUzJtpSnZP3s05Ji8K6a_NeaC16m52pOcYoL5moweUml6UxwmKoJl_Jgss-V3aqEwzqaxYeh2p9fvqNiX5nQ3UI2jn7BatxynA8xz4eCdduYMfmA-Sl51JtyeXZ3npHrD--vLy7rqy8fP13sr2rHJV9q2mILCh1abiQ4YZySncVe2Z4yIwTSnrO2azpnOui56RtrFNji0hrpenZG3h5l59VO2DkMSzKjnpOfTNp0NF7_3Qn-oIf4XSsOikooAq_uBFL8tmJe9OSzw3E0AeOaddPSVii2Y7KgL_9Bb-KaQnFXKCEVlKxooZoj5VLMOWF__xkK-meo-hiqLqHq21D1VoZe_GnjfuRXigVgRyCXVhgw_d79H9kf1VexJg</recordid><startdate>20210901</startdate><enddate>20210901</enddate><creator>Yang, Liping</creator><creator>Hou, Yixuan</creator><creator>Du, Yan-e</creator><creator>Li, Qiao</creator><creator>Zhou, Fanlin</creator><creator>Li, Yu</creator><creator>Zeng, Huan</creator><creator>Jin, Ting</creator><creator>Wan, Xueying</creator><creator>Guan, Shengdong</creator><creator>Wang, Rui</creator><creator>Liu, Manran</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3898-6878</orcidid></search><sort><creationdate>20210901</creationdate><title>Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines</title><author>Yang, Liping ; Hou, Yixuan ; Du, Yan-e ; Li, Qiao ; Zhou, Fanlin ; Li, Yu ; Zeng, Huan ; Jin, Ting ; Wan, Xueying ; Guan, Shengdong ; Wang, Rui ; Liu, Manran</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-15e508eceb4a70c6ac87dbef8bf13a66e1f435d2dcad0f4af2ba80b067ba7cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>13/1</topic><topic>13/105</topic><topic>13/51</topic><topic>13/89</topic><topic>13/95</topic><topic>14</topic><topic>38</topic><topic>38/61</topic><topic>38/77</topic><topic>42</topic><topic>45</topic><topic>45/15</topic><topic>59</topic><topic>631/45/320</topic><topic>631/67/322</topic><topic>64</topic><topic>82</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Cell Cycle Analysis</topic><topic>Chromosome 5</topic><topic>Cofilin</topic><topic>Gastric cancer</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Lipid metabolism</topic><topic>Lysophospholipids - metabolism</topic><topic>Male</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics - methods</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>miRNA</topic><topic>Monoacylglycerol Lipases - metabolism</topic><topic>Neoplasm Metastasis</topic><topic>Phosphatidylserine</topic><topic>RhoA protein</topic><topic>Stem Cells</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Transcription</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Liping</creatorcontrib><creatorcontrib>Hou, Yixuan</creatorcontrib><creatorcontrib>Du, Yan-e</creatorcontrib><creatorcontrib>Li, Qiao</creatorcontrib><creatorcontrib>Zhou, Fanlin</creatorcontrib><creatorcontrib>Li, Yu</creatorcontrib><creatorcontrib>Zeng, Huan</creatorcontrib><creatorcontrib>Jin, Ting</creatorcontrib><creatorcontrib>Wan, Xueying</creatorcontrib><creatorcontrib>Guan, Shengdong</creatorcontrib><creatorcontrib>Wang, Rui</creatorcontrib><creatorcontrib>Liu, Manran</creatorcontrib><collection>Springer Nature OA Free 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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death and differentiation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Liping</au><au>Hou, Yixuan</au><au>Du, Yan-e</au><au>Li, Qiao</au><au>Zhou, Fanlin</au><au>Li, Yu</au><au>Zeng, Huan</au><au>Jin, Ting</au><au>Wan, Xueying</au><au>Guan, Shengdong</au><au>Wang, Rui</au><au>Liu, Manran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines</atitle><jtitle>Cell death and differentiation</jtitle><stitle>Cell Death Differ</stitle><addtitle>Cell Death Differ</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>28</volume><issue>9</issue><spage>2708</spage><epage>2727</epage><pages>2708-2727</pages><issn>1350-9047</issn><eissn>1476-5403</eissn><abstract>The aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric cancer (GC) metastasis. MiR-4646-5p, one of Drosha-independent mirtronic miRNA, is aberrant up-regulated in Drosha-low expressed GC and Drosha-knockdown gastric cancer cells. Mirtronic miR-4646-5p is a specific transcription splicing product of intron 3 of the host gene
Abhd16a
with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate
Abhd16a
and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene
Abhd16a
mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33875796</pmid><doi>10.1038/s41418-021-00779-y</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0002-3898-6878</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell death and differentiation, 2021-09, Vol.28 (9), p.2708-2727 |
| issn | 1350-9047 1476-5403 |
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| source | MEDLINE; SpringerLink Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | 13/1 13/105 13/51 13/89 13/95 14 38 38/61 38/77 42 45 45/15 59 631/45/320 631/67/322 64 82 Animals Apoptosis Biochemistry Biomedical and Life Sciences Cell Biology Cell Cycle Analysis Chromosome 5 Cofilin Gastric cancer Humans Life Sciences Lipid metabolism Lysophospholipids - metabolism Male Metabolism Metabolites Metabolomics - methods Metastases Metastasis Mice Mice, Nude miRNA Monoacylglycerol Lipases - metabolism Neoplasm Metastasis Phosphatidylserine RhoA protein Stem Cells Stomach Neoplasms - genetics Stomach Neoplasms - pathology Transcription Transfection |
| title | Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines |
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