MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer

Cekaite, Lina; Eide, Peter W.; Lind, Guro Elisabeth; Skotheim, Rolf Inge; Lothe, Ragnhild

doi:10.18632/oncotarget.6390

Cited by 93 publications

(84 citation statements)

References 292 publications

(176 reference statements)

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“…MicroRNAs (miRNAs) are involved in the development and progression of malignant tumors, mainly through post-transcriptional modulation of oncogenic and tumor suppressor pathways and provide prognostic information [2, 9, 16, 18, 31, 40, 48]. In breast cancer, differential miRNA expression has been demonstrated across breast cancer subtypes, with both tumor-promoting and tumor-suppressive functions for individual miRNAs [5, 8, 15, 17, 23, 44].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

Raychaudhuri

Bronger

Buchner

et al. 2017

Breast Cancer Res Treat

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Purpose miRNAs have been linked to chemosensitivity of breast cancer cells in-vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response to neoadjuvant chemotherapy, and II) differential miRNA expression in residual tumor after completion of chemotherapy allows further prognostic stratification of non-responding patients. Methods Sixty-four patients with newly diagnosed large (≥3cm) or locally advanced primary breast cancers who underwent neoadjuvant anthracycline/taxane-based chemotherapy were included. Relative expression of 10 miRNAs likely to be associated with chemotherapy response (miR-7,-21,-29a,-29b,-34a,-125b,-155,-200c,-340,-451) was determined by quantitative RT-PCR from pretherapeutic biopsies (n=64) and residual invasive tumor after chemotherapy (n=42). Pathologic complete response (pCR) defined by absence of invasive tumor served as reference standard. In addition, miRNA expression was compared with disease-free and overall-survival. Results Nine (14%) of 64 patients achieved pCR. High expression of miR-7 and low expression of miR-340 in pretherapeutic biopsies predicted pCR with a negative-predictive-value of 96% and 97%, respectively (specificity 54% and 57%). The combined profile of miR-7high/miR-340low demonstrated improved specificity of 86% while maintaining a high negative-predictive-value (96%) to identify non-responders. Pretherapeutic expression of miR-200c and miR-155 showed prognostic information and low expression was associated with increased overall survival (115 vs. 90 months, p≤0.03). After chemotherapy, the overall survival of patients with residual invasive tumor was better for those demonstrating low miR-7 or high miR-125b (p=0.01). Conclusions Intratumoral expression of miR-7 and miR-340 prior to neoadjuvant chemotherapy could be used to predict pCR and a profile of miR-7low or miR-340high identified patients unlikely to achieve pCR who might benefit from alternative treatment options including earlier surgery. Our study identifies miRNAs as promising predictive biomarkers, which could aid in optimization of breast cancer management and treatment stratification.

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Section: Introductionmentioning

confidence: 99%

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

Raychaudhuri

Bronger

Buchner

et al. 2017

Breast Cancer Res Treat

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“…A growing body of evidence demonstrates that the abnormal expression of miRNAs might serve as a potential diagnostic and prognostic biomarker for cancers [14]. …”

Section: Discussionmentioning

confidence: 99%

Identification of the miRNA-mRNA regulatory network of small cell osteosarcoma based on RNA-seq

et al. 2017

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Small cell osteosarcoma (SCO) is a rare subtype of osteosarcoma characterized by highly aggressive progression and a poor prognosis. The miRNA and mRNA expression profiles of peripheral blood mononuclear cells (PBMCs) were obtained in 3 patients with SCO and 10 healthy individuals using high-throughput RNA-sequencing. We identified 37 dysregulated miRNAs and 1636 dysregulated mRNAs in patients with SCO compared to the healthy controls. Specifically, the 37 dysregulated miRNAs consisted of 27 up-regulated miRNAs and 10 down-regulated miRNAs; the 1636 dysregulated mRNAs consisted of 555 up-regulated mRNAs and 1081 down-regulated mRNAs. The target-genes of miRNAs were predicted, and 1334 negative correlations between miRNAs and mRNAs were used to construct an miRNA-mRNA regulatory network. Dysregulated genes were significantly enriched in pathways related to cancer, mTOR signaling and cell cycle signaling. Specifically, hsa-miR-26b-5p, hsa-miR-221-3p and hsa-miR-125b-2-3p were significantly dysregulated miRNAs and exhibited a high degree of connectivity with target genes. Overall, the expression of dysregulated genes in tumor tissues and peripheral blood samples of patients with SCO measured by quantitative real-time polymerase chain reaction corroborated with our bioinformatics analyses based on the expression profiles of PBMCs from patients with SCO. Thus, hsa-miR-26b-5p, hsa-miR-221-3p and hsa-miR-125b-2-3p may be involved in SCO tumorigenesis.

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“…MicroRNAs have been demonstrated to play critical roles in cell progressions of cancers in recent years [17, 18], but the expression and mechanism of some of them in LSCC remain unclear.…”

Section: Discussionmentioning

confidence: 99%

miR-375 and miR-205 Regulate the Invasion and Migration of Laryngeal Squamous Cell Carcinoma Synergistically via AKT-Mediated EMT

Wang

Chen

et al. 2016

BioMed Research International

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Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. However, the mechanisms of miR-375 and miR-205 regulating the invasion and migration of LSCC remain unknown. qRT-PCR was performed in 40 pairs of tissue samples to investigate the expression of miR-375 and miR-205 in LSCC and paracarcinoma tissues. To investigate whether or not miR-375 and miR-205 regulated the invasion and migration of LSCC synergistically via AKT-mediated epithelial-mesenchymal transition, miR-375 mimic and miR-205 inhibitor were transfected into SNU899 cells and miR-375 inhibitor and miR-205 mimic were transfected into SNU899 cells, respectively, with or without AKT inhibitor. Then the expressions of miR-375 and miR-205 were validated by qRT-PCR, cell migration and invasion were determined by wound healing assay and transwell invasive assay, and western blot analysis was performed to detect the expression of related proteins. Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. In conclusion, our findings provided not only new information about the molecular mechanism of miRNAs regulating invasion and migration of LSCC, but also a theoretical principle for potential targeting therapy of laryngeal squamous carcinoma.

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MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer

Cited by 93 publications

References 292 publications

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

Identification of the miRNA-mRNA regulatory network of small cell osteosarcoma based on RNA-seq

miR-375 and miR-205 Regulate the Invasion and Migration of Laryngeal Squamous Cell Carcinoma Synergistically via AKT-Mediated EMT

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