Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression

The present study aimed to investigate the interaction between miR-196 and its target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy (1,200 mg/m2 fluorouracil, 200 mg/m2 leucovorin...

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Published in:Oncology letters 2016-11, Vol.12 (5), p.4041-4047
Main Authors: Shen, Songfei, Pan, Jie, Lu, Xingrong, Chi, Pan
Format: Article
Language:English
Subjects:
Cancer
Cancer therapies
Chemotherapy
Colorectal cancer
Development and progression
Disease
Drug therapy
FOLFOX4
Gene expression
Genetic aspects
Health aspects
homeobox B8
Innovations
Lymphatic system
Metastasis
Methods
MicroRNA
miR-196
Molecular targeted therapy
neoadjuvant chemotherapy
Oncology
Patient outcomes
Polymerase chain reaction
Proteins
Studies
Surgery
Transcription factors
Tumors
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Lu, Xingrong
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description The present study aimed to investigate the interaction between miR-196 and its target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy (1,200 mg/m2 fluorouracil, 200 mg/m2 leucovorin and 85 mg/m2 oxaliplatin). In total, 80 tissue samples were collected in the present study. In total, 50 patients undergoing preoperative chemotherapy completed at least 3 cycles (2 weeks per cycle) of 85 mg/m2 oxaliplatin (day 1) combined with a 2 h injection of 200 mg/m2 leucovorin (days 1 and 2), a bolus injection of 400 mg/m2 and 44 h continuous intravenous infusion of 1,200 mg/m2 fluorouracil. Complete response and partial response were included in the chemotherapy sensitive group (25 patients), and stable disease and progressive disease were included in the chemotherapy resistant group (25 patients). In addition, 30 patients without preoperative chemotherapy were examined for mRNA and protein expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR-196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In addition, the expression of the mRNA and protein of miR-196 and HoxB8 was measured in 50 tissue samples obtained from patients that had received FOLFOX4 neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC tissues were significantly increased compared with the corresponding normal mucosa tissue (P
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In total, 80 tissue samples were collected in the present study. In total, 50 patients undergoing preoperative chemotherapy completed at least 3 cycles (2 weeks per cycle) of 85 mg/m2 oxaliplatin (day 1) combined with a 2 h injection of 200 mg/m2 leucovorin (days 1 and 2), a bolus injection of 400 mg/m2 and 44 h continuous intravenous infusion of 1,200 mg/m2 fluorouracil. Complete response and partial response were included in the chemotherapy sensitive group (25 patients), and stable disease and progressive disease were included in the chemotherapy resistant group (25 patients). In addition, 30 patients without preoperative chemotherapy were examined for mRNA and protein expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR-196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In addition, the expression of the mRNA and protein of miR-196 and HoxB8 was measured in 50 tissue samples obtained from patients that had received FOLFOX4 neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC tissues were significantly increased compared with the corresponding normal mucosa tissue (P&lt;0.05). The miR-196 mRNA was significantly correlated with lymph node metastasis, tumor stage and distant metastasis (P&lt;0.05). miR-196 was indicated to be negatively correlated with HoxB8 mRNA expression (r=−0.458; P&lt;0.05). The relative amount of miR-196 in the chemotherapy-sensitive group of patients was 0.949±0.691, which was increased compared with the chemotherapy-resistant group (0.345±0.536; P&lt;0.01). The relative level of HoxB8 mRNA in the chemotherapy-sensitive group was 0.490±0.372, which was decreaesd compared with the chemotherapy-resistant group (0.725±0.438; P&lt;0.05). HoxB8 protein expression level in the chemotherapy-sensitive group was decreased compared with the chemotherapy-resistant group (Z=−2.396; P=0.017). Overall, miR-196 was correlated with metastasis and prognosis, and HoxB8 was highly expressed in CRC tissues. The difference in the gene expression of miR-196 and HoxB8 may be associated with the sensitivity to FOLFOX4 for CRC patients. In addition, the highly expressed miR-196 increased the sensitivity of CRC cells to chemotherapy with FOLFOX4 by inhibiting HoxB8.</description><identifier>ISSN: 1792-1074</identifier><identifier>EISSN: 1792-1082</identifier><identifier>DOI: 10.3892/ol.2016.5210</identifier><identifier>PMID: 27895768</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Cancer ; Cancer therapies ; Chemotherapy ; Colorectal cancer ; Development and progression ; Disease ; Drug therapy ; FOLFOX4 ; Gene expression ; Genetic aspects ; Health aspects ; homeobox B8 ; Innovations ; Lymphatic system ; Metastasis ; Methods ; MicroRNA ; miR-196 ; Molecular targeted therapy ; neoadjuvant chemotherapy ; Oncology ; Patient outcomes ; Polymerase chain reaction ; Proteins ; Studies ; Surgery ; Transcription factors ; Tumors</subject><ispartof>Oncology letters, 2016-11, Vol.12 (5), p.4041-4047</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><rights>Copyright © 2016, Spandidos Publications 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-96f878697b770e623ed03999d37cb58492012484ffc8345c3c31febc391111013</citedby><cites>FETCH-LOGICAL-c539t-96f878697b770e623ed03999d37cb58492012484ffc8345c3c31febc391111013</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/PMC5104229/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104229/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27895768$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shen, Songfei</creatorcontrib><creatorcontrib>Pan, Jie</creatorcontrib><creatorcontrib>Lu, Xingrong</creatorcontrib><creatorcontrib>Chi, Pan</creatorcontrib><title>Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression</title><title>Oncology letters</title><addtitle>Oncol Lett</addtitle><description>The present study aimed to investigate the interaction between miR-196 and its target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy (1,200 mg/m2 fluorouracil, 200 mg/m2 leucovorin and 85 mg/m2 oxaliplatin). In total, 80 tissue samples were collected in the present study. In total, 50 patients undergoing preoperative chemotherapy completed at least 3 cycles (2 weeks per cycle) of 85 mg/m2 oxaliplatin (day 1) combined with a 2 h injection of 200 mg/m2 leucovorin (days 1 and 2), a bolus injection of 400 mg/m2 and 44 h continuous intravenous infusion of 1,200 mg/m2 fluorouracil. Complete response and partial response were included in the chemotherapy sensitive group (25 patients), and stable disease and progressive disease were included in the chemotherapy resistant group (25 patients). In addition, 30 patients without preoperative chemotherapy were examined for mRNA and protein expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR-196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In addition, the expression of the mRNA and protein of miR-196 and HoxB8 was measured in 50 tissue samples obtained from patients that had received FOLFOX4 neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC tissues were significantly increased compared with the corresponding normal mucosa tissue (P&lt;0.05). The miR-196 mRNA was significantly correlated with lymph node metastasis, tumor stage and distant metastasis (P&lt;0.05). miR-196 was indicated to be negatively correlated with HoxB8 mRNA expression (r=−0.458; P&lt;0.05). The relative amount of miR-196 in the chemotherapy-sensitive group of patients was 0.949±0.691, which was increased compared with the chemotherapy-resistant group (0.345±0.536; P&lt;0.01). The relative level of HoxB8 mRNA in the chemotherapy-sensitive group was 0.490±0.372, which was decreaesd compared with the chemotherapy-resistant group (0.725±0.438; P&lt;0.05). HoxB8 protein expression level in the chemotherapy-sensitive group was decreased compared with the chemotherapy-resistant group (Z=−2.396; P=0.017). Overall, miR-196 was correlated with metastasis and prognosis, and HoxB8 was highly expressed in CRC tissues. The difference in the gene expression of miR-196 and HoxB8 may be associated with the sensitivity to FOLFOX4 for CRC patients. In addition, the highly expressed miR-196 increased the sensitivity of CRC cells to chemotherapy with FOLFOX4 by inhibiting HoxB8.</description><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Drug therapy</subject><subject>FOLFOX4</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>homeobox B8</subject><subject>Innovations</subject><subject>Lymphatic system</subject><subject>Metastasis</subject><subject>Methods</subject><subject>MicroRNA</subject><subject>miR-196</subject><subject>Molecular targeted therapy</subject><subject>neoadjuvant chemotherapy</subject><subject>Oncology</subject><subject>Patient outcomes</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Studies</subject><subject>Surgery</subject><subject>Transcription factors</subject><subject>Tumors</subject><issn>1792-1074</issn><issn>1792-1082</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNptklFrFDEQxxdRbKl981kCivjgnclmN5u8FGrxrHBwUBR8C7ns7G1KNlmT3bP9YH4_s3f17ImTh4TML_9hJv8se0nwnHKRf_B2nmPC5mVO8JPslFQinxHM86eHc1WcZOcx3uIUJSOcs-fZSV5xUVaMn2a_brwF5BvUmZsZEQwpVyMzRDSosIEBbcABuvZ3HzkyDg0toBq2YH3fgRt2cB-8NQ0ENRjvJqV27JRD2lsfQA_KIq2chrCDJwHT9UoPE-nAq_p23KokpVvofEoH1d-jn2Zo0WK1XKy-F8jv6pqA4K4PEGMq8yJ71igb4fxhP8u-LT59vbqeLVefv1xdLme6pGKYCdbwijNRrasKA8sp1JgKIWpa6XXJC5Fmlxe8aBrNaVFqqilpYK2pICkwoWfZxV63H9cd1Dr1HJSVfTCdCvfSKyOPM860cuO3siS4yHORBN49CAT_Y4Q4yM5EDdaq1PsYJeFFwTAr-IS-_ge99WNwqT1JBM0ZS2T1l9ooC9K4xqe6ehKVl0VFKacVwYma_4dKq4bOaO-gMen-6MHbRw9aUHZoo7fj9KfxGHy_B3XwMQZoDsMgWE6WlN7KyZJysmTCXz0e4AH-Y8AEvNkDsU_-MLWPB2a1nOG0djq_AdsR5rM</recordid><startdate>20161101</startdate><enddate>20161101</enddate><creator>Shen, Songfei</creator><creator>Pan, Jie</creator><creator>Lu, Xingrong</creator><creator>Chi, Pan</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</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>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161101</creationdate><title>Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression</title><author>Shen, Songfei ; Pan, Jie ; Lu, Xingrong ; Chi, Pan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-96f878697b770e623ed03999d37cb58492012484ffc8345c3c31febc391111013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Colorectal cancer</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Drug therapy</topic><topic>FOLFOX4</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>homeobox B8</topic><topic>Innovations</topic><topic>Lymphatic system</topic><topic>Metastasis</topic><topic>Methods</topic><topic>MicroRNA</topic><topic>miR-196</topic><topic>Molecular targeted therapy</topic><topic>neoadjuvant chemotherapy</topic><topic>Oncology</topic><topic>Patient outcomes</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>Studies</topic><topic>Surgery</topic><topic>Transcription factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shen, Songfei</creatorcontrib><creatorcontrib>Pan, Jie</creatorcontrib><creatorcontrib>Lu, Xingrong</creatorcontrib><creatorcontrib>Chi, Pan</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection (ProQuest Medical &amp; Health Databases)</collection><collection>ProQuest Central (purchase pre-March 2016)</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)</collection><collection>ProQuest Central</collection><collection>British Nursing Database</collection><collection>AUTh Library subscriptions: 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 &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shen, Songfei</au><au>Pan, Jie</au><au>Lu, Xingrong</au><au>Chi, Pan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression</atitle><jtitle>Oncology letters</jtitle><addtitle>Oncol Lett</addtitle><date>2016-11-01</date><risdate>2016</risdate><volume>12</volume><issue>5</issue><spage>4041</spage><epage>4047</epage><pages>4041-4047</pages><issn>1792-1074</issn><eissn>1792-1082</eissn><abstract>The present study aimed to investigate the interaction between miR-196 and its target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy (1,200 mg/m2 fluorouracil, 200 mg/m2 leucovorin and 85 mg/m2 oxaliplatin). In total, 80 tissue samples were collected in the present study. In total, 50 patients undergoing preoperative chemotherapy completed at least 3 cycles (2 weeks per cycle) of 85 mg/m2 oxaliplatin (day 1) combined with a 2 h injection of 200 mg/m2 leucovorin (days 1 and 2), a bolus injection of 400 mg/m2 and 44 h continuous intravenous infusion of 1,200 mg/m2 fluorouracil. Complete response and partial response were included in the chemotherapy sensitive group (25 patients), and stable disease and progressive disease were included in the chemotherapy resistant group (25 patients). In addition, 30 patients without preoperative chemotherapy were examined for mRNA and protein expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR-196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In addition, the expression of the mRNA and protein of miR-196 and HoxB8 was measured in 50 tissue samples obtained from patients that had received FOLFOX4 neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC tissues were significantly increased compared with the corresponding normal mucosa tissue (P&lt;0.05). The miR-196 mRNA was significantly correlated with lymph node metastasis, tumor stage and distant metastasis (P&lt;0.05). miR-196 was indicated to be negatively correlated with HoxB8 mRNA expression (r=−0.458; P&lt;0.05). The relative amount of miR-196 in the chemotherapy-sensitive group of patients was 0.949±0.691, which was increased compared with the chemotherapy-resistant group (0.345±0.536; P&lt;0.01). The relative level of HoxB8 mRNA in the chemotherapy-sensitive group was 0.490±0.372, which was decreaesd compared with the chemotherapy-resistant group (0.725±0.438; P&lt;0.05). HoxB8 protein expression level in the chemotherapy-sensitive group was decreased compared with the chemotherapy-resistant group (Z=−2.396; P=0.017). Overall, miR-196 was correlated with metastasis and prognosis, and HoxB8 was highly expressed in CRC tissues. The difference in the gene expression of miR-196 and HoxB8 may be associated with the sensitivity to FOLFOX4 for CRC patients. In addition, the highly expressed miR-196 increased the sensitivity of CRC cells to chemotherapy with FOLFOX4 by inhibiting HoxB8.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>27895768</pmid><doi>10.3892/ol.2016.5210</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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1792-1082
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5104229
source PubMed Central
subjects Cancer
Cancer therapies
Chemotherapy
Colorectal cancer
Development and progression
Disease
Drug therapy
FOLFOX4
Gene expression
Genetic aspects
Health aspects
homeobox B8
Innovations
Lymphatic system
Metastasis
Methods
MicroRNA
miR-196
Molecular targeted therapy
neoadjuvant chemotherapy
Oncology
Patient outcomes
Polymerase chain reaction
Proteins
Studies
Surgery
Transcription factors
Tumors
title Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression
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