MicroRNAs as Cancer Players: Potential Clinical and Biological Effects

Bandrés, Eva; Agirre, Xabier; Ramírez, Natalia; Zárate, Ruth; Garcı́a-Foncillas, Jesús

doi:10.1089/dna.2006.0544

Cited by 60 publications

(53 citation statements)

References 98 publications

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“…Interestingly, recent studies have documented a link between the aberrant expression of a class of small noncoding RNAs (17-28 nucleotides), termed microRNAs (miRNA), and the pathogenesis of several cancer types including CRC (12)(13)(14). MiRNAs negatively regulate gene expression at the posttranscriptional level by cleavage and/or translational repression of their mRNA targets and their dysregulation is believed to promote the malignant behavior of tumors (12).…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer

et al. 2008

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MicroRNAs (miRNA) are a class of small noncoding RNAs with important posttranscriptional regulatory functions. Recent data suggest that miRNAs are aberrantly expressed in many human cancers and that they may play significant roles in carcinogenesis. Here, we used microarrays to profile the expression of 315 human miRNAs in 10 normal mucosa samples and 49 stage II colon cancers differing with regard to microsatellite status and recurrence of disease. Several miRNAs were differentially expressed between normal tissue and tumor microsatellite subtypes, with miR-145 showing the lowest expression in cancer relative to normal tissue. Microsatellite status for the majority of cancers could be correctly predicted based on miRNA expression profiles. Furthermore, a biomarker based on miRNA expression profiles could predict recurrence of disease with an overall performance accuracy of 81%, indicating a potential role of miRNAs in determining tumor aggressiveness. The expression levels of miR-320 and miR-498, both included in the predictive biomarker, correlated with the probability of recurrence-free survival by multivariate analysis. We successfully verified the expression of selected miRNAs using real-time reverse transcription-PCR assays for mature miRNAs, whereas in situ hybridization was used to detect the accumulation of miR-145 and miR-320 in normal epithelial cells and adenocarcinoma cells. Functional studies showed that miR-145 potently suppressed growth of three different colon carcinoma cell lines. In conclusion, our results suggest that perturbed expression of numerous miRNAs in colon cancer may have a functional effect on tumor cell behavior, and, furthermore, that some miRNAs with prognostic potential could be of clinical importance. [Cancer Res 2008;68(15):6416-24]

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Section: Introductionmentioning

confidence: 99%

Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer

et al. 2008

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“…Several studies have documented a link between the aberrant expression of a class of small non-coding RNAs, termed microRNAs (miRNAs), and the pathogenesis/prognosis of several cancer types, including colorectal cancer (4,5). These molecules provide a potentially valuable diagnostic/prognostic tool for CRC pathology, because mature miRNA species are relatively more stable than mRNAs and well preserved in formalin-fixed, paraffin-embedded samples which are commonly used in clinical routine (6).…”

Section: Introductionmentioning

confidence: 99%

miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer

Akçakaya

Ekelund²,

Kolosenko³

et al. 2011

Int J Oncol

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Abstract. Colorectal cancer (CRC) is one of the most common and deadly forms of cancer. Despite improved treatment modalities, post-operative recurrence and metastasis remain the major problems for extending patient survival after surgery. This highlights the need to search for biomarkers for prognostication and treatment stratification of colorectal cancer patients. In this study, we applied the SYBR-green quantitative PCR-based array approach to screen for differentially expressed miRNAs between patients with short (<50 months, range 10-33 months) and long survival (≥50 months, range 50-152 months). The selected candidate prognostic miRNAs were validated in a cohort of 50 CRC patients by TaqMan quantitative PCR. We found that high expression of miR-185 and low expression of miR-133b were correlated with poor survival (p=0.001 and 0.028, respectively) and metastasis (p=0.007 and 0.036, respectively) in colorectal cancer. Our findings suggest the potential prognostic values of these miRNAs for predicting clinical outcome after surgery. IntroductionColorectal cancer (CRC) is the second most common cancer in women and the third in men worldwide (1). It ranks the second most common cause of cancer death in the Western world (2). Currently, there are several treatment modalities for CRC, including surgery, radiotherapy, chemotherapy and targeted therapy (e.g., cetuximab). However, the long-term survival remains low in metastatic disease (3).Given that CRC usually follows a stepwise progression from benign to malignant lesion and distant metastasis, there is a possibility for early diagnosis in order to reduce morbidity and mortality. The commonly used method to characterize CRC tumor in clinic is T1-T3 staging system. However, the staging system reflects only morphological characteristics of the tumor and does not consider tumor molecular biology, thus, it is inaccurate in predicting the future outcome for each particular case. Therefore, the development of screening tools and new biomarkers to facilitate early diagnosis is particularly warranted. Further investigations in the search for new prognostic biomarkers may help to improve post-operative treatment approaches for CRC patients.Several studies have documented a link between the aberrant expression of a class of small non-coding RNAs, termed microRNAs (miRNAs), and the pathogenesis/prognosis of several cancer types, including colorectal cancer (4,5). These molecules provide a potentially valuable diagnostic/prognostic tool for CRC pathology, because mature miRNA species are relatively more stable than mRNAs and well preserved in formalin-fixed, paraffin-embedded samples which are commonly used in clinical routine (6). Furthermore, only a small number of miRNAs are required to distinguish cancerous tissues from non-cancerous tissues compared with mRNA profiles (7), which makes them more feasible candidate biomarkers.miRNAs are endogenous single-stranded non-coding RNAs of ~22-nucleotides in length, which are generated by an RNase III enzyme Dicer from endogenou...

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“…Emerging evidence suggests that miRNAs may play important roles in cancer (15)(16)(17). miRNAs can function as both oncogenes and tumor suppressors in their effect on tumor growth (18,19). Recent data demonstrate that miRNAs are important factors in stem cell biology and in the determination of cell fate (20)(21)(22) whereas the knowledge on miRNAs expression in liver CSCs is still preliminary.…”

Section: Introductionmentioning

confidence: 99%

microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb

Zhang

Luo²,

Luo³

et al. 2011

Int J Oncol

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Abstract. MicroRNAs (miRNAs) have been implicated in the maintenance of the cancer stem cell (CSC) phenotype via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Thus, identification of CSC-related miRNAs would provide information for a better understanding of CSCs. Here, we compared the miRNA profiles of CD133 + and CD133 -primary hepatocellular carcinoma (HCC) subpopulations and found upregulation of 5 miRNAs in CD133 -subpopulations, including hsa-miR-150, which may be involved in maintenance of the CD133 + liver CSC phenotype. We also show that miR-150 interacts with the 3'UTR of c-Myb mRNA and overexpression of miR-150 downregulates c-Myb protein levels. Furthermore, overexpression of miR-150 lead to a significant reduction of CD133 + cells, accompanied by significant inhibition of cell growth and tumorsphere formation. In addition, overexpression of miR-150 induces cell cycle arrest and apoptosis in CD133 + cells. Consistent with the outcome of cell cycle arrest and cell apoptosis, Western blotting results demonstrate that the cell cycle regulator cyclin D1 and cell survival regulator Bcl-2 are decreased in cells transfected with miR-150. Collectively, our findings demonstrate for the first time that miR-150 may be involved in liver CSC self-renewal, potentially via modulation of the downstream target c-Myb.

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MicroRNAs as Cancer Players: Potential Clinical and Biological Effects

Cited by 60 publications

References 98 publications

Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer

Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer

miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer

microRNA-150 inhibits human CD133-positive liver cancer stem cells through negative regulation of the transcription factor c-Myb

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