TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000371222
  • Gene Name:JUN
  • mRNA database:Ensembl
  • mRNA expression :up-regulated
  • mRNA Method:qRT-PCR
  • mRNA Pathway:NA
  • Evidence:predicted
  • (mRNA-drug)

Drug basic information

  • Drug ID:NA
  • Drug Name:NA
  • Drug Method:NA

Disease basic infommation

  • Disease:colorectal cancer
  • Tissue:The human colorectal cancer HCT8, HCT116 parental cell lines, gastric cancer SGC7901, and hepatic carcinoma Bel7402 parental cell lines

Other information

  • Title:miR200c attenuates P-gp-mediated MDR and metastasis by targeting JNK2/c-Jun signaling pathway in colorectal cancer.
  • Journal:Molecular cancer therapeutics
  • Published:2014
  • PubMed ID:25205654
  • Abstract: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.
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