MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways
Increasing evidence indicates that dysregulation of miR-195 may contribute to the occurrence and development of multiple types of human malignancies. However, the function and the mechanism of miR-195 in clear cell renal cell carcinoma (ccRCC) are still not fully understood. In the present study, we...
Gespeichert in:
Veröffentlicht in: | International journal of oncology 2016-09, Vol.49 (3), p.1155-1163 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1163 |
---|---|
container_issue | 3 |
container_start_page | 1155 |
container_title | International journal of oncology |
container_volume | 49 |
creator | Sun, Pengcheng Wang, Lu Lu, Yunhan Liu, Yuwei Li, Lechen Yin, Luyao Zhang, Cheng Zhao, Weiming Shen, Baozhong Xu, Wanhai |
description | Increasing evidence indicates that dysregulation of miR-195 may contribute to the occurrence and development of multiple types of human malignancies. However, the function and the mechanism of miR-195 in clear cell renal cell carcinoma (ccRCC) are still not fully understood. In the present study, we used qRT-PCR to detect the expression of miR-195 in ccRCC tissues and normal kidney tissues. MTT assay was performed to detect the cell viability of miR-195. Migration and invasion were evaluated by Transwell migration and Matrigel invasion assays, respectively. Additionally, apoptosis levels were evaluated using TUNEL assays, and signaling pathway changes were determined by western blot analysis. We observed that miR-195 was downregulated in clear cell renal cell carcinoma samples compared with normal renal samples. We identified that overexpression of miR-195 inhibited ACHN cell viability, migration, invasion, and it also induced cell apoptosis by targeting VEGFR2 via PI3K/Akt and Raf/MEK/ERK signaling pathways. These findings indicate that miR-195 has a tumor suppressive role in ACHN cells and miR-195 may be a promising candidate target for prevention and treatment of renal cell carcinoma. |
doi_str_mv | 10.3892/ijo.2016.3608 |
format | Article |
fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_1932323413</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A463756421</galeid><sourcerecordid>A463756421</sourcerecordid><originalsourceid>FETCH-LOGICAL-c490t-d034eeb9359ea03c243b5cd0709d4690365dd0e2e265f2967f64cf10702209853</originalsourceid><addsrcrecordid>eNptkV1v0zAUhiMEYmNwyS2yhARXaf2d-jKqug91G6gCbi03cVqXJM58nKHt18-lYzAJnQtbPs975KMny94TPGEzRadu5ycUEzlhEs9eZMekUCSnnLKX6Y6JyiVn6ih7A7DDmAqByevsiBaioLRgx9n9lauCX12XOVECRRM2NgL6sTg7XVFk-hptDSCD4tj5gGAchmAB3K1FwbcWuR6V8_NrVNm2BXTrDPp6wZbT8mf8nV2ZZnq1WE4XqyUCt-lN6_oNGkzc_jJ38DZ71ZgW7LvH8yT7frr4Nj_PL7-cXczLy7ziCse8xoxbu1ZMKGswqyhna1HVuMCq5lJhJkVdY0stlaKhShaN5FVDUp9SrGaCnWQfD3OH4G9GC1Hv_BjSZ0ATxWgqTthfamNaq13f-BhM1TmodMklK4TklCRq8h8qVW07V_neNi69Pwt8-iewtaaNW_DtGJ3v4TmYH8CkAyDYRg_BdSbcaYL13rROpvXetN6bTvyHx63GdWfrJ_qP2gR8PgAwJBeu9vDEpEk5VzlmOSFCsAelVaqY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1932323413</pqid></control><display><type>article</type><title>MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways</title><source>Spandidos Publications Journals</source><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Sun, Pengcheng ; Wang, Lu ; Lu, Yunhan ; Liu, Yuwei ; Li, Lechen ; Yin, Luyao ; Zhang, Cheng ; Zhao, Weiming ; Shen, Baozhong ; Xu, Wanhai</creator><creatorcontrib>Sun, Pengcheng ; Wang, Lu ; Lu, Yunhan ; Liu, Yuwei ; Li, Lechen ; Yin, Luyao ; Zhang, Cheng ; Zhao, Weiming ; Shen, Baozhong ; Xu, Wanhai</creatorcontrib><description>Increasing evidence indicates that dysregulation of miR-195 may contribute to the occurrence and development of multiple types of human malignancies. However, the function and the mechanism of miR-195 in clear cell renal cell carcinoma (ccRCC) are still not fully understood. In the present study, we used qRT-PCR to detect the expression of miR-195 in ccRCC tissues and normal kidney tissues. MTT assay was performed to detect the cell viability of miR-195. Migration and invasion were evaluated by Transwell migration and Matrigel invasion assays, respectively. Additionally, apoptosis levels were evaluated using TUNEL assays, and signaling pathway changes were determined by western blot analysis. We observed that miR-195 was downregulated in clear cell renal cell carcinoma samples compared with normal renal samples. We identified that overexpression of miR-195 inhibited ACHN cell viability, migration, invasion, and it also induced cell apoptosis by targeting VEGFR2 via PI3K/Akt and Raf/MEK/ERK signaling pathways. These findings indicate that miR-195 has a tumor suppressive role in ACHN cells and miR-195 may be a promising candidate target for prevention and treatment of renal cell carcinoma.</description><identifier>ISSN: 1019-6439</identifier><identifier>EISSN: 1791-2423</identifier><identifier>DOI: 10.3892/ijo.2016.3608</identifier><identifier>PMID: 27572273</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>ACHN ; Angiogenesis ; Apoptosis ; Cancer therapies ; Carcinoma, Renal cell ; Carcinoma, Renal Cell - genetics ; Care and treatment ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell Movement ; clear cell renal cell carcinoma ; Development and progression ; Down-Regulation ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Genetic aspects ; Health aspects ; Humans ; Innovations ; Kidney cancer ; Kidney Neoplasms - genetics ; Male ; MAP Kinase Signaling System ; Medical research ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miR-195 ; Molecular targeted therapy ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Properties ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Tumor suppressor genes ; Vascular Endothelial Growth Factor Receptor-2 - genetics ; VEGFR2</subject><ispartof>International journal of oncology, 2016-09, Vol.49 (3), p.1155-1163</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-d034eeb9359ea03c243b5cd0709d4690365dd0e2e265f2967f64cf10702209853</citedby><cites>FETCH-LOGICAL-c490t-d034eeb9359ea03c243b5cd0709d4690365dd0e2e265f2967f64cf10702209853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,5571,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27572273$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Pengcheng</creatorcontrib><creatorcontrib>Wang, Lu</creatorcontrib><creatorcontrib>Lu, Yunhan</creatorcontrib><creatorcontrib>Liu, Yuwei</creatorcontrib><creatorcontrib>Li, Lechen</creatorcontrib><creatorcontrib>Yin, Luyao</creatorcontrib><creatorcontrib>Zhang, Cheng</creatorcontrib><creatorcontrib>Zhao, Weiming</creatorcontrib><creatorcontrib>Shen, Baozhong</creatorcontrib><creatorcontrib>Xu, Wanhai</creatorcontrib><title>MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways</title><title>International journal of oncology</title><addtitle>Int J Oncol</addtitle><description>Increasing evidence indicates that dysregulation of miR-195 may contribute to the occurrence and development of multiple types of human malignancies. However, the function and the mechanism of miR-195 in clear cell renal cell carcinoma (ccRCC) are still not fully understood. In the present study, we used qRT-PCR to detect the expression of miR-195 in ccRCC tissues and normal kidney tissues. MTT assay was performed to detect the cell viability of miR-195. Migration and invasion were evaluated by Transwell migration and Matrigel invasion assays, respectively. Additionally, apoptosis levels were evaluated using TUNEL assays, and signaling pathway changes were determined by western blot analysis. We observed that miR-195 was downregulated in clear cell renal cell carcinoma samples compared with normal renal samples. We identified that overexpression of miR-195 inhibited ACHN cell viability, migration, invasion, and it also induced cell apoptosis by targeting VEGFR2 via PI3K/Akt and Raf/MEK/ERK signaling pathways. These findings indicate that miR-195 has a tumor suppressive role in ACHN cells and miR-195 may be a promising candidate target for prevention and treatment of renal cell carcinoma.</description><subject>ACHN</subject><subject>Angiogenesis</subject><subject>Apoptosis</subject><subject>Cancer therapies</subject><subject>Carcinoma, Renal cell</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement</subject><subject>clear cell renal cell carcinoma</subject><subject>Development and progression</subject><subject>Down-Regulation</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Innovations</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - genetics</subject><subject>Male</subject><subject>MAP Kinase Signaling System</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>miR-195</subject><subject>Molecular targeted therapy</subject><subject>Neoplasm Invasiveness</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Properties</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Tumor suppressor genes</subject><subject>Vascular Endothelial Growth Factor Receptor-2 - genetics</subject><subject>VEGFR2</subject><issn>1019-6439</issn><issn>1791-2423</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkV1v0zAUhiMEYmNwyS2yhARXaf2d-jKqug91G6gCbi03cVqXJM58nKHt18-lYzAJnQtbPs975KMny94TPGEzRadu5ycUEzlhEs9eZMekUCSnnLKX6Y6JyiVn6ih7A7DDmAqByevsiBaioLRgx9n9lauCX12XOVECRRM2NgL6sTg7XVFk-hptDSCD4tj5gGAchmAB3K1FwbcWuR6V8_NrVNm2BXTrDPp6wZbT8mf8nV2ZZnq1WE4XqyUCt-lN6_oNGkzc_jJ38DZ71ZgW7LvH8yT7frr4Nj_PL7-cXczLy7ziCse8xoxbu1ZMKGswqyhna1HVuMCq5lJhJkVdY0stlaKhShaN5FVDUp9SrGaCnWQfD3OH4G9GC1Hv_BjSZ0ATxWgqTthfamNaq13f-BhM1TmodMklK4TklCRq8h8qVW07V_neNi69Pwt8-iewtaaNW_DtGJ3v4TmYH8CkAyDYRg_BdSbcaYL13rROpvXetN6bTvyHx63GdWfrJ_qP2gR8PgAwJBeu9vDEpEk5VzlmOSFCsAelVaqY</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Sun, Pengcheng</creator><creator>Wang, Lu</creator><creator>Lu, Yunhan</creator><creator>Liu, Yuwei</creator><creator>Li, Lechen</creator><creator>Yin, Luyao</creator><creator>Zhang, Cheng</creator><creator>Zhao, Weiming</creator><creator>Shen, Baozhong</creator><creator>Xu, Wanhai</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20160901</creationdate><title>MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways</title><author>Sun, Pengcheng ; Wang, Lu ; Lu, Yunhan ; Liu, Yuwei ; Li, Lechen ; Yin, Luyao ; Zhang, Cheng ; Zhao, Weiming ; Shen, Baozhong ; Xu, Wanhai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-d034eeb9359ea03c243b5cd0709d4690365dd0e2e265f2967f64cf10702209853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>ACHN</topic><topic>Angiogenesis</topic><topic>Apoptosis</topic><topic>Cancer therapies</topic><topic>Carcinoma, Renal cell</topic><topic>Carcinoma, Renal Cell - genetics</topic><topic>Care and treatment</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement</topic><topic>clear cell renal cell carcinoma</topic><topic>Development and progression</topic><topic>Down-Regulation</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Innovations</topic><topic>Kidney cancer</topic><topic>Kidney Neoplasms - genetics</topic><topic>Male</topic><topic>MAP Kinase Signaling System</topic><topic>Medical research</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>miR-195</topic><topic>Molecular targeted therapy</topic><topic>Neoplasm Invasiveness</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Properties</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Tumor suppressor genes</topic><topic>Vascular Endothelial Growth Factor Receptor-2 - genetics</topic><topic>VEGFR2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Pengcheng</creatorcontrib><creatorcontrib>Wang, Lu</creatorcontrib><creatorcontrib>Lu, Yunhan</creatorcontrib><creatorcontrib>Liu, Yuwei</creatorcontrib><creatorcontrib>Li, Lechen</creatorcontrib><creatorcontrib>Yin, Luyao</creatorcontrib><creatorcontrib>Zhang, Cheng</creatorcontrib><creatorcontrib>Zhao, Weiming</creatorcontrib><creatorcontrib>Shen, Baozhong</creatorcontrib><creatorcontrib>Xu, Wanhai</creatorcontrib><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>Proquest Nursing & Allied Health Source</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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><jtitle>International journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Pengcheng</au><au>Wang, Lu</au><au>Lu, Yunhan</au><au>Liu, Yuwei</au><au>Li, Lechen</au><au>Yin, Luyao</au><au>Zhang, Cheng</au><au>Zhao, Weiming</au><au>Shen, Baozhong</au><au>Xu, Wanhai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways</atitle><jtitle>International journal of oncology</jtitle><addtitle>Int J Oncol</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>49</volume><issue>3</issue><spage>1155</spage><epage>1163</epage><pages>1155-1163</pages><issn>1019-6439</issn><eissn>1791-2423</eissn><abstract>Increasing evidence indicates that dysregulation of miR-195 may contribute to the occurrence and development of multiple types of human malignancies. However, the function and the mechanism of miR-195 in clear cell renal cell carcinoma (ccRCC) are still not fully understood. In the present study, we used qRT-PCR to detect the expression of miR-195 in ccRCC tissues and normal kidney tissues. MTT assay was performed to detect the cell viability of miR-195. Migration and invasion were evaluated by Transwell migration and Matrigel invasion assays, respectively. Additionally, apoptosis levels were evaluated using TUNEL assays, and signaling pathway changes were determined by western blot analysis. We observed that miR-195 was downregulated in clear cell renal cell carcinoma samples compared with normal renal samples. We identified that overexpression of miR-195 inhibited ACHN cell viability, migration, invasion, and it also induced cell apoptosis by targeting VEGFR2 via PI3K/Akt and Raf/MEK/ERK signaling pathways. These findings indicate that miR-195 has a tumor suppressive role in ACHN cells and miR-195 may be a promising candidate target for prevention and treatment of renal cell carcinoma.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>27572273</pmid><doi>10.3892/ijo.2016.3608</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1019-6439 |
ispartof | International journal of oncology, 2016-09, Vol.49 (3), p.1155-1163 |
issn | 1019-6439 1791-2423 |
language | eng |
recordid | cdi_proquest_journals_1932323413 |
source | Spandidos Publications Journals; MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | ACHN Angiogenesis Apoptosis Cancer therapies Carcinoma, Renal cell Carcinoma, Renal Cell - genetics Care and treatment Cell cycle Cell growth Cell Line, Tumor Cell Movement clear cell renal cell carcinoma Development and progression Down-Regulation Female Gene expression Gene Expression Regulation, Neoplastic Genetic aspects Health aspects Humans Innovations Kidney cancer Kidney Neoplasms - genetics Male MAP Kinase Signaling System Medical research Metastasis MicroRNA MicroRNAs MicroRNAs - genetics miR-195 Molecular targeted therapy Neoplasm Invasiveness Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Properties Proteins Proto-Oncogene Proteins c-akt - metabolism Tumor suppressor genes Vascular Endothelial Growth Factor Receptor-2 - genetics VEGFR2 |
title | MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-01T04%3A59%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=MicroRNA-195%20targets%20VEGFR2%20and%20has%20a%20tumor%20suppressive%20role%20in%20ACHN%20cells%20via%20PI3K/Akt%20and%20Raf/MEK/ERK%20signaling%20pathways&rft.jtitle=International%20journal%20of%20oncology&rft.au=Sun,%20Pengcheng&rft.date=2016-09-01&rft.volume=49&rft.issue=3&rft.spage=1155&rft.epage=1163&rft.pages=1155-1163&rft.issn=1019-6439&rft.eissn=1791-2423&rft_id=info:doi/10.3892/ijo.2016.3608&rft_dat=%3Cgale_proqu%3EA463756421%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1932323413&rft_id=info:pmid/27572273&rft_galeid=A463756421&rfr_iscdi=true |