A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD
Hua Hu,1 Linlin Zhang,1 Geling Teng,1 Yanhua Wu,1 Ying Chen2 1The Respiratory Department, Shandong Provincial Chest Hospital, 2The Clinical Laboratory of Shandong Provincial Chest Hospital, Jinan, Shandong, People’s Republic of China Objective: The objective of the present study was to exp...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2015-08-01
|
Series: | International Journal of COPD |
Online Access: | http://www.dovepress.com/a-variant-in-339-untranslated-region-of-kras-compromises-its-interacti-peer-reviewed-article-COPD |
_version_ | 1818517205349826560 |
---|---|
author | Hu H Zhang L Teng G Wu Y Chen Y |
author_facet | Hu H Zhang L Teng G Wu Y Chen Y |
author_sort | Hu H |
collection | DOAJ |
description | Hua Hu,1 Linlin Zhang,1 Geling Teng,1 Yanhua Wu,1 Ying Chen2 1The Respiratory Department, Shandong Provincial Chest Hospital, 2The Clinical Laboratory of Shandong Provincial Chest Hospital, Jinan, Shandong, People’s Republic of China Objective: The objective of the present study was to explore the molecular mechanism by which a single nucleotide polymorphism (rs712) interferes with interaction between 3'-untranslated region (3'-UTR) of KRAS and let-7g, and its association with development of lung cancer in the patients with COPD.Materials and methods: In this study, we confirmed that KRAS is a target of let-7g in lung cancer cells, and that introduction of rs712 minor allele into 3'-UTR significantly compromised the miRNA/mRNA interaction by using a luciferase reporter system. Additionally, a total of 35 lung tissue samples were obtained (TT:17, TG:12, GG:6), and let-7g and KRAS expression levels were determined.Results: We showed that let-7g level was similar between groups, and the concentration of KRAS in GG genotype group was significantly higher than in TT or GT genotype group. Meanwhile, we found COPD patients with GG genotype had significantly higher risk for lung cancer (odds ratio OR =6.83, P=0.0081), compared with TT and GT genotypes.Conclusion: Our study demonstrated that KRAS 3'-UTR rs712 polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of lung cancer in COPD. Keywords: let-7g, chronic obstructive pulmonary disease, lung cancer, KRAS, single nucleotide polymorphism |
first_indexed | 2024-12-11T00:53:02Z |
format | Article |
id | doaj.art-a4228df316174355b3b17c479b57f2fd |
institution | Directory Open Access Journal |
issn | 1178-2005 |
language | English |
last_indexed | 2024-12-11T00:53:02Z |
publishDate | 2015-08-01 |
publisher | Dove Medical Press |
record_format | Article |
series | International Journal of COPD |
spelling | doaj.art-a4228df316174355b3b17c479b57f2fd2022-12-22T01:26:34ZengDove Medical PressInternational Journal of COPD1178-20052015-08-012015Issue 11641164923177A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPDHu HZhang LTeng GWu YChen YHua Hu,1 Linlin Zhang,1 Geling Teng,1 Yanhua Wu,1 Ying Chen2 1The Respiratory Department, Shandong Provincial Chest Hospital, 2The Clinical Laboratory of Shandong Provincial Chest Hospital, Jinan, Shandong, People’s Republic of China Objective: The objective of the present study was to explore the molecular mechanism by which a single nucleotide polymorphism (rs712) interferes with interaction between 3'-untranslated region (3'-UTR) of KRAS and let-7g, and its association with development of lung cancer in the patients with COPD.Materials and methods: In this study, we confirmed that KRAS is a target of let-7g in lung cancer cells, and that introduction of rs712 minor allele into 3'-UTR significantly compromised the miRNA/mRNA interaction by using a luciferase reporter system. Additionally, a total of 35 lung tissue samples were obtained (TT:17, TG:12, GG:6), and let-7g and KRAS expression levels were determined.Results: We showed that let-7g level was similar between groups, and the concentration of KRAS in GG genotype group was significantly higher than in TT or GT genotype group. Meanwhile, we found COPD patients with GG genotype had significantly higher risk for lung cancer (odds ratio OR =6.83, P=0.0081), compared with TT and GT genotypes.Conclusion: Our study demonstrated that KRAS 3'-UTR rs712 polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of lung cancer in COPD. Keywords: let-7g, chronic obstructive pulmonary disease, lung cancer, KRAS, single nucleotide polymorphismhttp://www.dovepress.com/a-variant-in-339-untranslated-region-of-kras-compromises-its-interacti-peer-reviewed-article-COPD |
spellingShingle | Hu H Zhang L Teng G Wu Y Chen Y A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD International Journal of COPD |
title | A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD |
title_full | A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD |
title_fullStr | A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD |
title_full_unstemmed | A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD |
title_short | A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD |
title_sort | variant in 3 39 untranslated region of kras compromises its interaction with hsa let 7g and nbsp contributes to the development of lung cancer in nbsp patients with copd |
url | http://www.dovepress.com/a-variant-in-339-untranslated-region-of-kras-compromises-its-interacti-peer-reviewed-article-COPD |
work_keys_str_mv | AT huh avariantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT zhangl avariantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT tengg avariantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT wuy avariantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT cheny avariantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT huh variantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT zhangl variantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT tengg variantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT wuy variantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd AT cheny variantin339untranslatedregionofkrascompromisesitsinteractionwithhsalet7gandnbspcontributestothedevelopmentoflungcancerinnbsppatientswithcopd |