KRAS alleles: the LCS6 3'UTR variant and KRAS coding sequence mutations in the NCI-60 panel.
ABSTRACT The KRAS-variant is a germline single nucleotide polymorphism (SNP) within the 3'UTR of the KRAS gene predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA (miRNA). The KRAS-variant is associated with increased risk of various cancers, including lung cancer, ovarian cancer and triple-negative breast cancer, and is associated with altered tumor biology in head and neck cancer, colon cancer and melanoma. To better understand the molecular pathways that may be regulated or affected by the presence of the KRAS-variant allele in cancer cells, we examined its prevalence in the NCI-60 panel of cell lines and sought to identify common features of the cell lines that carry the variant allele. This study provides a step forward towards understanding the molecular and pathological significance of the KRAS-variant.
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ABSTRACT: Despite common belief, accumulation of molecular damage does not play a key role in aging. Still, cancer (an age-related disease) is initiated by molecular damage. Cancer and aging share a lot in common including the activation of the TOR pathway. But the role of molecular damage distinguishes cancer and aging. Furthermore, an analysis of the role of both damage and aging in cancer argues against "a decline, caused by accumulation of molecular damage" as a cause of aging. I also discuss how random molecular damage, via rounds of multiplication and selection, brings about non-random hallmarks of cancer.Aging 12/2011; 3(12):1130-41. · 4.89 Impact Factor
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ABSTRACT: Single-nucleotide polymorphisms within microRNA (miRNA) binding sites comprise a novel genre of cancer biomarkers. Since miRNA regulation is dependent on sequence complementarity between the mRNA transcript and the miRNA, even single-nucleotide aberrations can have significant effects. Over the past few years, many examples of these functional miRNA binding site SNPs have been identified as cancer biomarkers. While most of the research to date focuses on associations with cancer risk, more and more studies are linking these SNPs to cancer prognosis and response to treatment as well. This review summarizes the state of the field and draws importance to this rapidly expanding area of cancer biomarkers.Critical reviews in oncogenesis 01/2013; 18(4):327-40. DOI:10.1615/CritRevOncog.2013007254
Article: MicroRNAs in malignant melanoma.[Show abstract] [Hide abstract]
ABSTRACT: Melanoma is the most aggressive form of skin cancer, and the incidence of melanoma has been increasing faster than that of most other cancers. While the survival rate following surgical resection of early-stage primary tumors is nearly 100%, the survival of patients with metastasized tumors is strongly reduced, likely due to resistance to conventional therapies. Therefore, it is important to use new molecular approaches to develop new biomarkers to better prevent and diagnose melanoma. MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally regulate gene expression via repression of translation or direct degradation of their complementary mRNA. In this review, we summarize our current understanding of the involvement of miRNAs and their corresponding targets in melanomagenesis as well as the potential use of miRNAs as biomarkers.Clinical biochemistry 01/2013; DOI:10.1016/j.clinbiochem.2013.01.008 · 2.23 Impact Factor