MicroRNA profiling predicts survival in anti-EGFR treated chemorefractory metastatic colorectal cancer patients with wild-type KRAS and BRAF

Mosakhani, Neda; Lahti, Leo; Borze, Ioana; Karjalainen–Lindsberg, Marja-Liisa; Sundström, Jari; Ristamäki, Raija; Österlund, Pia; Knuutila, Sakari; Sarhadi, Virinder

doi:10.1016/j.cancergen.2012.08.003

Cited by 68 publications

(65 citation statements)

References 32 publications

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“…Although miR-140-5p is generally regarded as a tumor suppressor in many human malignancies, previous studies have showed a discrepancy for its role in cancer development depending on different cell context [13,14,26]. A progressive loss of miR-140-5p has been well demonstrated from normal colorectal mucosa to primary CRC tissues in a study by Zhai et al [14], with further reduction in liver metastatic tissues.…”

Section: Discussionmentioning

confidence: 85%

“…Higher miR-140-5p expression is significantly correlated with better survival in stage III and IV CRC patients. In contrast, Mosakhani and colleague found that miR-140-5p up-regulation were significantly associated with poorer overall survival in metastatic CRC patients with wild type KRAS/BRAF [26]. Song et al showed that miR-140-5p is downregulated in CRC tissue compare with adjacent normal tissue, but is upregulated in colon cancer stem-like cells [13].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Zhang

Zou

Pan

et al. 2015

Cell Physiol Biochem

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Background: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. Methods: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. Results: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. Conclusions: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Zhang

Zou

Pan

et al. 2015

Cell Physiol Biochem

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“…Some of these patients were a part of previously published study (32). All patients in this training set were considered refractory to a 5-fluorouracil-based regimen combined with irinotecan and oxaliplatin.…”

Section: Patientsmentioning

confidence: 99%

Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy

Manceau

Imbeaud

Thiébaut

et al. 2014

Clinical Cancer Research

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Purpose: To identify microRNAs (miRNA) that predict response to anti-EGFR antibodies in patients with wild-type KRAS metastatic colorectal cancer (mCRC).Experimental Design: miRNA profiling was performed in a training set of 87 patients with mCRC refractory to chemotherapy treated with anti-EGFR antibodies. This included 33 fresh-frozen (FF) and 35 formalin-fixed paraffin-embedded (FFPE) samples retrospectively collected and 19 prospectively collected FF samples. An independent validation cohort consisting of 19 FF and 26 FFPE prospectively collected samples from patients with mCRC treated with anti-EGFR antibodies was used to confirm our findings.Results: After screening the expression of 1,145 miRNAs in FF samples from the training set, we identified that hsa-miR-31-3p expression level was significantly associated with progression-free survival (PFS). Statistical models based on miRNA expression discriminated between high and low risk of progression for both FF and FFPE samples. These models were confirmed in the validation cohort for both FF [HR, 4.1; 95% confidence interval (CI), 1.1-15.3; P < 0.04] and FFPE samples (HR, 2.44; 95% CI, 1.1-5.4; P ¼ 0.028). The percentage of variation of RECIST criteria in the validation series was significantly associated with the expression level of hsa-miR-31-3p (r 2 ¼ 0.49; P ¼ 0.0035) and risk status determined by hsa-miR-31-3p expression level (P ¼ 0.02, Kruskal-Wallis rank test). Nomograms were built and validated to predict PFSdepending on hsa-miR-31-3p expression level. Following in vitro studies, we identified 47 genes regulated by hsa-miR-31-3p. Conclusion: Hsa-miR-31-3p seems to be a new mCRC biomarker whose expression level allows for the identification of patients with wild-type KRAS mCRC who are more likely to respond to anti-EGFR therapy.

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“…Thus it is likely that miR-494 directly interacts with DRA 3=-UTR and suppresses the corresponding protein product. While we were at a juncture to complete our miR-494 studies, a report in the literature (36) indicated that DRA suppression in metastatic colorectal cancer patients was via upregulation of miR-31*. This conclusion was based on their microarray results.…”

Section: Discussionmentioning

confidence: 95%

“…While we were preparing this article, a recent report suggested that miR-31* could play a role in modulating DRA expression (36). To investigate a possible direct involvement of miR-31*, we cotransfected mimic-31* with 3=-UTR of DRA in Caco-2 cells.…”

Section: Resultsmentioning

confidence: 99%

Translational repression of SLC26A3 by miR-494 in intestinal epithelial cells

Anbazhagan

Priyamvada

Kumar

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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[downregulated in adenoma (DRA)] is a Cl Ϫ /HCO 3 Ϫ exchanger involved in electroneutral NaCl absorption in the mammalian intestine. Altered DRA expression levels are associated with infectious and inflammatory diarrheal diseases. Therefore, it is critical to understand the regulation of DRA expression. MicroRNAs (miRNAs) are endogenous, small RNAs that regulate protein expression via blocking the translation and/or promoting mRNA degradation. To investigate potential modulation of DRA expression by miRNA, five different in silico algorithms were used to predict the miRNAs that target DRA. Of these miRNAs, miR-494 was shown to have a highly conserved putative binding site in the DRA 3=-untranslated region (3=-UTR) compared with other DRA-targeting miRNAs in vertebrates. Transfection with pmirGLO dual luciferase vector containing DRA 3=-UTR (pmirGLO-3=-UTR DRA) resulted in a significant decrease in relative luciferase activity compared with empty vector. Cotransfection of the DRA 3=-UTR luciferase vector with a miR-494 mimic further decreased luciferase activity compared with cells transfected with negative control. The transfection of a miR-494 mimic into Caco-2 and T-84 cells significantly increased the expression of miR-494 and concomitantly decreased the DRA protein expression. Mutation of the seed sequences for miR-494 in 3=-UTR of DRA abrogated the effect of miR-494 on 3=-UTR. These data demonstrate a novel regulatory mechanism of DRA expression via miR-494 and indicate that targeting this microRNA may serve to be a potential therapeutic strategy for diarrheal diseases.

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MicroRNA profiling predicts survival in anti-EGFR treated chemorefractory metastatic colorectal cancer patients with wild-type KRAS and BRAF

Cited by 68 publications

References 32 publications

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

Hsa-miR-31-3p Expression Is Linked to Progression-free Survival in Patients with KRAS Wild-type Metastatic Colorectal Cancer Treated with Anti-EGFR Therapy

Translational repression of SLC26A3 by miR-494 in intestinal epithelial cells

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