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Restoration of mutant K-Ras repressed miR-199b inhibits K-Ras mutant non-small cell lung cancer progression
DC Field | Value | Language |
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dc.contributor.author | Jin, Hua | - |
dc.contributor.author | Jang, Yoonjeong | - |
dc.contributor.author | Cheng, Nian | - |
dc.contributor.author | Li, Qing | - |
dc.contributor.author | Cui, Peng-Fei | - |
dc.contributor.author | Zhou, Zhi-Wei | - |
dc.contributor.author | Jiang, Hu-Lin | - |
dc.contributor.author | Cho, Myung-Haing | - |
dc.contributor.author | Westover, Kenneth D. | - |
dc.contributor.author | Tan, Qun-You | - |
dc.contributor.author | Xu, Cheng-Xiong | - |
dc.date.accessioned | 2019-05-13T02:19:15Z | - |
dc.date.available | 2019-05-13T11:20:06Z | - |
dc.date.created | 2019-10-22 | - |
dc.date.created | 2019-10-22 | - |
dc.date.issued | 2019-04 | - |
dc.identifier.citation | Journal of Experimental & Clinical Cancer Research, Vol.38 No.1, p. 165 | - |
dc.identifier.issn | 1756-9966 | - |
dc.identifier.other | 85312 | - |
dc.identifier.uri | https://hdl.handle.net/10371/153246 | - |
dc.description.abstract | Background: miRNAs play crucial role in the progression of K-Ras-mutated nonsmall cell lung cancer (NSCLC). However, most studies have focused on miRNAs that target K-Ras. Here, we investigated miRNAs regulated by mutant K-Ras and their functions. Methods: miRNAs regulated by mutant K-Ras were screened using miRNA arrays. miR-199b expression levels were measured by qRT-PCR. The protein expression levels were measured using Western blot and immunohistochemistry. The effects of miR-199b on NSCLC were examined both in vitro and in vivo by overexpressing or inhibiting miR-199b. DNA methylation was measured by bisulfite sequencing. Results: An inverse correlation was observed between K-Ras mutation status and miR-199b levels in NSCLC specimens and cell lines. The inhibition of miR-199b stimulated NSCLC growth and metastasis, while restoration of miR-199b suppressed K-Ras mutation-driven lung tumorigenesis as well as K-Ras-mutated NSCLC growth and metastasis. miR-199b inactivated ERK and Akt pathways by targeting K-Ras, KSR2, PIK3R1, Akt1, and Rheb1. Furthermore, we determined that mutant K-Ras inhibits miR-199b expression by increasing miR-199b promoter methylation. Conclusion: Our findings suggest that mutant K-Ras plays an oncogenic role through downregulating miR-199b in NSCLC and that overexpression of miR-199b is a novel strategy for the treatment of K-Ras-mutated NSCLC. | - |
dc.language | 영어 | - |
dc.language.iso | en | ko_KR |
dc.publisher | BioMed Central Ltd. | - |
dc.title | Restoration of mutant K-Ras repressed miR-199b inhibits K-Ras mutant non-small cell lung cancer progression | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 조명행 | - |
dc.identifier.doi | 10.1186/s13046-019-1170-7 | - |
dc.citation.journaltitle | Journal of Experimental & Clinical Cancer Research | - |
dc.identifier.wosid | 000465468400005 | - |
dc.identifier.scopusid | 2-s2.0-85064396909 | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s). | - |
dc.date.updated | 2019-04-21T03:19:18Z | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 165 | - |
dc.citation.volume | 38 | - |
dc.identifier.sci | 000465468400005 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Cho, Myung-Haing | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | TARGETS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MICRORNA-199B-5P | - |
dc.subject.keywordPlus | ADENOCARCINOMA | - |
dc.subject.keywordPlus | SUPPRESSION | - |
dc.subject.keywordPlus | METASTASIS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | TRANSITION | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordAuthor | miR-199b | - |
dc.subject.keywordAuthor | K-Ras | - |
dc.subject.keywordAuthor | Non-small cell lung cancer | - |
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