Underexpression of miR-224 in methotrexate resistant human colon cancer cells

Mencia, Núria; Selga, Elisabet; Noé, Verónique; Ciudad, Carlos J.

doi:10.1016/j.bcp.2011.08.009

Cited by 80 publications

(60 citation statements)

References 53 publications

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“…miR-224 is an independent prognostic marker in cervical cancer and lung cancer too [17, 19, 32]. On the other hand, Mencia et al demonstrated that miR-224 underexpression leads to insensitivity towards methotrexate, favoring a resistant phenotype [18]. In glioblastoma, miR-224 overexpression increases radiation sensitivity, thus improving outcomes, and patients with high miR-224 expression levels reportedly have a better overall survival [20].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma

Cavedon

Barollo

Bertazza

et al. 2017

International Journal of Endocrinology

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Little is known about the function of microRNA-224 (miR-224) in medullary thyroid cancer (MTC). This study investigated the role of miR-224 expression in MTC and correlated it with mutation status in sporadic MTCs. A consecutive series of 134 MTCs were considered. Patients had a sporadic form in 80% of cases (107/134). In this group, REarranged during transfection (RET) and rat sarcoma (RAS) mutation status were assessed by direct sequencing in the tumor tissues. Quantitative real-time polymerase chain reaction was used to quantify mature hsa-miR-224 in tumor tissue. RAS (10/107 cases, 9%) and RET (39/107 cases, 36%) mutations were mutually exclusive in sporadic cases. miR-224 expression was significantly downregulated in patients with the following: high calcitonin levels at diagnosis (p = 0.03, r = −0.3); advanced stage (p = 0.001); persistent disease (p = 0.001); progressive disease (p = 0.002); and disease-related death (p = 0.0001). We found a significant positive correlation between miR-224 expression and somatic RAS mutations (p = 0.007). Patients whose MTCs had a low miR-224 expression tended to have a shorter overall survival (log-rank test p = 0.005). On multivariate analysis, miR-224 represented an independent prognostic marker. Our data indicate that miR-224 is upregulated in RAS-mutated MTCs and in patients with a better prognosis and could represent an independent prognostic marker in MTC patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma

Cavedon

Barollo

Bertazza

et al. 2017

International Journal of Endocrinology

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“…Yet, reports that methotrexate-resistant colon cancer cells express lower miR-224 [23], and that miR-224 suppresses tumor growth and metastasis in vivo [20] suggest that an opposite role in CRC may be true. The latter study also showed lower miR-224 expression in metastatic CRC cell lines versus non-metastatic cell lines, and in metastatic tumors in the lung versus primary CRC tumors [20].…”

Section: Discussionmentioning

confidence: 99%

The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis

Ling

Pickard

Ivan

et al. 2015

Gut

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Objective MicroRNA (miRNA) expression profile can be used as prognostic marker for human cancers. We aim to explore the significance of miRNAs in colorectal cancer (CRC) metastasis. Design We performed miRNA microarrays using primary CRC tissues from patients with and without metastasis, and validated selected candidates in 85 CRC samples by qRT-PCR. We tested metastatic activity of selected miRNAs, and identified miRNA targets by prediction algorithms, qRT-PCR, western blot and luciferase assays. Clinical outcomes were analyzed in six sets of CRC cases (n=449) including The Cancer Genome Atlas consortium and correlated with miR-224 status. We used the Kaplan-Meier method and log-rank test to assess the difference in survival between patients with low or high levels of miR-224 expression. Results MiR-224 expression increases consistently with tumor burden and microsatellite stable (MSS) status, and miR-224 enhances CRC metastasis in vitro and in vivo. We identified SMAD4 as a miR-224 target, and observed negative correlation (Spearman Rs=−0.44, p<0.0001) between SMAD4 and miR-224 expression in clinical samples. Patients with high miR-224 levels display shorter overall survival in multiple CRC cohorts (p=0.0259, 0.0137, 0.0207, 0.0181, 0.0331 and 0.0037 respectively), and shorter metastasis-free survival (hazard ratio 6.51, 95% CI 1.97-21.51, p=0.0008). In the TCGA set, combined analysis of miR-224 with SMAD4 expression enhanced correlation with survival (hazard ratio 4.12, 95% CI 1.1-15.41, p=0.0175). Conclusion MiR-224 promotes CRC metastasis, at least in part, through the regulation of SMAD4. MiR-224 expression in primary CRC, alone or combined with its targets, may have prognostic value for CRC patient survival.

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“…MiR-224 relates to methotrexate (MTX) resistance via targeting CDS2, HSPC159, and SLC4A4 in colon cancer. MiR-224-induced downregulation of CDS2, HSPC159, and SLC4A4 leads to increasing MTX sensitivity [55]. MiR-224 relates to the effect of celastrol on the inhibition of migration and invasion of HCC Cells.…”

Section: Clinical Significance Of Mir-224mentioning

confidence: 99%

MicroRNA-224: as a potential target for miR-based therapy of cancer

et al. 2015

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MicroRNAs (miRNAs) are small noncoding RNA molecules which regulate the target gene expression posttranscriptionally. Increasing studies have shown that microRNAs play important roles in multiple biological pathways. For instance, aberrant expression of microRNA-224 (miR-224) plays a vital role in tumor biology in various types of human cancer. Here, we aim to summarize the molecular mechanisms that lead to the overexpression of miR-224 in cancers, analyze the effect of miR-224 on tumor biology, and reveal the clinical significance of miR-224. MiR-224 regulates its targets by modulating messenger RNA (mRNA) stability and/or protein translation, and it would provide new insight into molecular targeting cancer treatment.

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Underexpression of miR-224 in methotrexate resistant human colon cancer cells

Cited by 80 publications

References 53 publications

Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma

Prognostic Impact of miR-224 and RAS Mutations in Medullary Thyroid Carcinoma

The clinical and biological significance of MIR-224 expression in colorectal cancer metastasis

MicroRNA-224: as a potential target for miR-based therapy of cancer

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