RGD Reference Report - miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer. - Rat Genome Database

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miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer.

Authors: Sui, Hua  Cai, Guo-Xiang  Pan, Shu-Fang  Deng, Wan-Li  Wang, Yu-Wei  Chen, Zhe-Sheng  Cai, San-Jun  Zhu, Hui-Rong  Li, Qi 
Citation: Sui H, etal., Mol Cancer Ther. 2014 Dec;13(12):3137-51. doi: 10.1158/1535-7163.MCT-14-0167. Epub 2014 Sep 9.
RGD ID: 13217416
Pubmed: PMID:25205654   (View Abstract at PubMed)
DOI: DOI:10.1158/1535-7163.MCT-14-0167   (Journal Full-text)

MicroRNA-200c (miR200c) recently emerged as an important regulator of tumorigenicity and cancer metastasis; however, its role in regulating multidrug resistance (MDR) remains unknown. In the current study, we found that the expression levels of miR200c in recurrent and metastatic colorectal cancers were significantly lower, whereas the JNK2 expression was higher compared with primary tumors. We showed that in MDR colorectal cancer cells, miR200c targeted the 3' untranslated region of the JNK2 gene. Overexpression of miR200c attenuated the levels of p-JNK, p-c-Jun, P-gp, and MMP-2/-9, the downstream factors of the JNK signaling pathway, resulting in increased sensitivity to chemotherapeutic drugs, which was accompanied by heightened apoptosis and decreased cell invasion and migration. Moreover, in an orthotopic MDR colorectal cancer mouse model, we demonstrated that overexpression of miR200c effectively inhibited the tumor growth and metastasis. At last, in the tumor samples from patients with locally advanced colorectal cancer with routine postsurgical chemotherapy, we observed an inverse correlation between the levels of mRNA expression of miR200c and JNK2, ABCB1, and MMP-9, thus predicting patient therapeutic outcomes. In summary, we found that miR200c negatively regulated the expression of JNK2 gene and increased the sensitivity of MDR colorectal cancer cells to chemotherapeutic drugs, via inhibiting the JNK2/p-JNK/p-c-Jun/ABCB1 signaling. Restoration of miR200c expression in MDR colorectal cancer may serve as a promising therapeutic approach in MDR-induced metastasis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colorectal cancer treatmentIDA 13217416 RGD 
colorectal cancer treatmentIEP 13217416 RGD 
colorectal cancer treatmentISOMAPK9 (Homo sapiens)13217416; 13217416 RGD 
colorectal cancer treatmentISOMIR200C (Homo sapiens)13217416; 13217416 RGD 
Neoplasm Metastasis  IEP 13217416associated with Colorectal NeoplasmsRGD 
Neoplasm Metastasis  ISOMAPK9 (Homo sapiens)13217416; 13217416associated with Colorectal NeoplasmsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Mapk9  (mitogen-activated protein kinase 9)
Mir200c  (microRNA 200c)

Genes (Mus musculus)
Mapk9  (mitogen-activated protein kinase 9)
Mir200c  (microRNA 200c)

Genes (Homo sapiens)
MAPK9  (mitogen-activated protein kinase 9)
MIR200C  (microRNA 200c)


Additional Information